» www.Giftbox.Az - Bir birindən gözəl hədiyyə satışı
ウィキペディアランダム
毎日カテゴリ
共有: WhatsappFacebookTwitterVK

KLF4

KLF4（Kruppel like factor 4）は、ジンクフィンガー型転写因子である(KLFファミリー)（英語版）の一員である。KLFファミリーはSp1様転写因子とともにSp1-like/KLFファミリーを構成する転写因子群である[5][6][7]。KLF4は細胞増殖、分化、アポトーシス、体細胞のリプログラミングの調節に関与している。また、KLF4は大腸がんなど特定のがんでがん抑制因子として機能することを示唆する証拠が得られている[8]。KLF4のC末端には3つのC2H2型ジンクフィンガーが存在し、これらは(KLF2)（英語版）と密接な関係にある[6]。また、2つの核局在配列が存在し、KLF4を細胞核へ局在させるシグナルとなっている[9]。胚性幹細胞では、KLF4は幹細胞性の良い指標となることが実証されている。このことは、間葉系幹細胞にも当てはまる。

KLF4
PDBに登録されている構造
PDBオルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧

2WBS, 2WBU, 4M9E

識別子
記号KLF4, EZF, GKLF, Kruppel-like factor 4 (gut), Kruppel like factor 4
外部IDOMIM: 602253 MGI: 1342287 HomoloGene: 3123 GeneCards: KLF4
遺伝子の位置 (ヒト)
染色体(9番染色体 (ヒト))[1]
バンドデータ無し開始点107,484,852 bp[1]
終点107,490,482 bp[1]
遺伝子の位置 (マウス)
染色体4番染色体 (マウス)[2]
バンドデータ無し開始点55,527,143 bp[2]
終点55,532,466 bp[2]
RNA発現パターン


さらなる参照発現データ
遺伝子オントロジー
分子機能• DNA結合
• sequence-specific DNA binding
• beta-catenin binding
• phosphatidylinositol 3-kinase regulator activity
• DNA-binding transcription factor activity
• zinc ion binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• 転写因子結合
• cis-regulatory region sequence-specific DNA binding
• 金属イオン結合
• RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity
• 血漿タンパク結合
• 核酸結合
• 二本鎖DNA結合
• promoter-specific chromatin binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• DNA-binding transcription factor activity, RNA polymerase II-specific
• transcription coregulator binding
• ヒストンデアセチラーゼ結合
細胞の構成要素• 細胞質
• transcription regulator complex
• 核質
• クロマチン
• 細胞核
生物学的プロセス• negative regulation of chemokine (C-X-C motif) ligand 2 production
• epidermal cell differentiation
• cellular response to retinoic acid
• negative regulation of protein kinase B signaling
• negative regulation of muscle hyperplasia
• negative regulation of smooth muscle cell proliferation
• positive regulation of protein metabolic process
• negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
• regulation of axon regeneration
• cellular response to peptide
• regulation of transcription, DNA-templated
• positive regulation of hemoglobin biosynthetic process
• response to retinoic acid
• somatic stem cell population maintenance
• cellular response to laminar fluid shear stress
• regulation of transcription by RNA polymerase II
• 細胞分化
• epidermis morphogenesis
• positive regulation of nitric oxide biosynthetic process
• cellular response to growth factor stimulus
• cellular response to organic cyclic compound
• post-embryonic hemopoiesis
• negative regulation of transcription by RNA polymerase II
• transcription by RNA polymerase II
• 有機物への反応
• 遺伝子発現の負の調節
• negative regulation of response to cytokine stimulus
• transcription, DNA-templated
• negative regulation of DNA-binding transcription factor activity
• negative regulation of phosphatidylinositol 3-kinase signaling
• stem cell population maintenance
• negative regulation of cell migration involved in sprouting angiogenesis
• positive regulation of gene expression
• negative regulation of cell migration
• regulation of cell population proliferation
• post-embryonic camera-type eye development
• regulation of phosphatidylinositol 3-kinase activity
• positive regulation of telomerase activity
• canonical Wnt signaling pathway
• negative regulation of ERK1 and ERK2 cascade
• regulation of cell differentiation
• mesodermal cell fate determination
• negative regulation of heterotypic cell-cell adhesion
• negative regulation of transcription, DNA-templated
• negative regulation of NF-kappaB transcription factor activity
• cellular response to cycloheximide
• negative regulation of inflammatory response
• fat cell differentiation
• positive regulation of transcription by RNA polymerase II
• negative regulation of cell population proliferation
• cellular response to hydrogen peroxide
• negative regulation of leukocyte adhesion to arterial endothelial cell
• positive regulation of core promoter binding
• cellular response to leukemia inhibitory factor
• negative regulation of angiogenesis
• pri-miRNA transcription by RNA polymerase II
• negative regulation of G1/S transition of mitotic cell cycle
• positive regulation of transcription, DNA-templated
• positive regulation of sprouting angiogenesis
出典:Amigo / QuickGO
オルソログ
種ヒトマウス
Entrez

9314

16600

Ensembl

ENSG00000136826

ENSMUSG00000003032

UniProt

O43474

Q60793

RefSeq
(mRNA)

NM_001314052
NM_004235

NM_010637

RefSeq
(タンパク質)

NP_001300981
NP_004226

NP_034767

場所
(UCSC)		Chr 9: 107.48 – 107.49 MbChr 9: 55.53 – 55.53 Mb
PubMed検索[3][4]
ウィキデータ
閲覧/編集 ヒト閲覧/編集 マウス

ヒトのKLF4タンパク質はKLF4遺伝子にコードされ、513アミノ酸からなり、約55 kDaと推定される[10]。KLF4遺伝子はチンパンジー、アカゲザル、イヌ、ウシ、マウス、ラット、ニワトリ、ゼブラフィッシュの間で保存されている[10]。KLF4は1996年に初めて同定された[11]。

相互作用

KLF4はN末端領域を介してp300/CBPコアクチベーターファミリーと相互作用し、転写を活性化することができる[12][13][14][15]。一方、KLF4による転写抑制は、アクチベーターの標的DNAへの結合に対しKLF4が競合することで行われる[16][17][18][19]。

KLF4はテロメラーゼの酵素サブユニット（TERT）のプロモーター領域に存在することも示されており、そこではβ-カテニンと複合体を形成している。KLF4はTERTのプロモーター領域へのβ-カテニンの蓄積に必要であるが、β-カテニンが存在しない場合にはTERTの発現を促進することはできない[20]。

機能

KLF4は多様な機能を持ち、その機能の一部は見かけ上矛盾したようなものであること、そして何より人工多能性幹細胞（iPS細胞）の誘導に必要不可欠な4つの因子のうちの1つとして重要な役割を果たしていることが発見されたことにより、近年大きな関心を集めている[21][22]。KLF4は非分裂細胞で高度に発現しており、その過剰発現は細胞周期の停止を誘導する[11][23][24][25][26]。KLF4はDNAが損傷した際の細胞分裂の阻害に特に重要である[23][25][26][27]。また、KLF4は中心体や染色体の数の調節（遺伝的安定性）や[28][29][30]、細胞の生存の促進にも重要である[31][31][32][33][34][35][36]。しかしながら、KLF4は特定の条件下では細胞生存促進から細胞死促進へ、その機能を切り替えている可能性が一部の研究で明らかにされている[35][37][38][39]。

KLF4は(腸管上皮)（英語版）において細胞分裂を行っていない細胞や終末分化した細胞で発現しており、腸管上皮の恒常性（さまざまな腸管上皮細胞種の終末分化と適切な局在）の調節に重要な役割を果たしている[40][41][42][43]。腸管上皮においては、KLF4は分化を調節するWntシグナル経路の遺伝子の重要な調節因子である[43]。

KLF4は他にもさまざまな組織や器官で発現している。角膜ではKLF4は上皮バリア機能に必要であり[44][45]、角膜の恒常性の維持に必要な遺伝子の調節因子である[46]。皮膚でも透過バリア機能の構築に必要であり[47][48][49]、骨や歯の組織では正常な骨格の発達を調節している[50][51][52][53]。マウスの生殖器の上皮細胞でも発現しており[54]、オスでは適切な精子形成に重要である[55][56][57]。血管内皮細胞では炎症刺激に応答した血管漏出の防止に重要であり[58][59]、血液細胞では炎症応答や細胞分化[60][61][62][63]、増殖[63][64]を媒介している。腎臓に関しては、in vitroにおける胚性幹細胞やiPS細胞の腎臓系統への分化に関与しており[65]、KLF4の調節異常はいくつかの腎臓疾患と関連している[66][67][68]。

疾患における役割

KLF4の疾患における役割は状況依存的であり、状況によって正反対の役割を果たす可能性があることが示されている。

KLF4は抗腫瘍形成因子であり、大腸がん[69]、胃がん[70]、食道扁平上皮がん[32]、小腸がん[71]、前立腺がん[72]、膀胱がん[73]、肺がん[74]など、ヒトのさまざまながんにおいて発現が喪失していることが多い。しかしながら、一部のがんではKLF4が腫瘍のプロモーションに関与している可能性があり、口腔扁平上皮がん[75]や原発性乳管がん[76]などではKLF4の発現は増大している。また、皮膚でのKLF4の過剰発現は過形成や異形成を引き起こし[77]、扁平上皮がんの発生につながる[78]。同様の知見は食道上皮でも得られており、マウスではKLF4の過剰発現は炎症の増大を引き起こし、最終的には食道扁平上皮がんの発生につながる[79]。

上皮間葉転換（EMT）におけるKLF4の役割に関しても議論がある。膵臓がん[80][81][82]、頭頸部がん[83]、子宮体がん[84]、上咽頭がん（英語版）[85]、前立腺がん[86]、非小細胞肺がん[87]では、KLF4はがん細胞の幹細胞性の維持や促進を刺激することが示されている。一方で、前立腺がん[88]や膵臓がん[89]などKLF4がEMTを促進することが示されている系においても、TGF-β誘導性のEMT条件下ではKLF4がEMTを抑制することが示されている。さらに、皮膚がん[90]、乳がん[35]、肺がん[91]、シスプラチン抵抗性上咽頭がん[92]では、KLF4がEMTを抑制することが示されている。

KLF4はいくつかの血管疾患で重要な役割を果たしており、マクロファージの極性化[93]やアテローム性動脈硬化におけるプラーク形成[94][95][96]を制御することで血管の炎症を調節することが示されている。KLF4は、抗アテローム性因子であるアポリポプロテインEをアップレギュレーションする[95]。また、KLF4は血管新生の調節にも関与している。KLF4は(NOTCH1)（英語版）の活性を調節することで血管新生を抑制している可能性がある一方で、中枢神経系ではKLF4の過剰発現は血管の異形成を引き起こす[97]。

マウスのマクロファージ[18]、食道上皮[79]、そして薬剤起因性大腸炎[98]などにおいては、KLF4がNF-κB依存的な炎症経路を介して炎症を促進している可能性が示されている。しかしながら、炎症促進刺激に応答した内皮細胞などではKLF4が炎症シグナルの活性化を抑制ている可能性が示されている[58]。

KLF4はDNA損傷に対する細胞応答に必要不可欠である。KLF4はガンマ線照射によるDNA損傷後の有糸分裂への進行の阻害に必要であり[25][26]、DNA修復機構を促進し、照射細胞のプログラム細胞死（アポトーシス）を防ぐ[31][33][34]。腸管上皮特異的にKLF4を欠失したマウスではガンマ線照射後の腸管上皮の再生が行われず、致死率が増加することから、この応答におけるKLF4の重要性がin vivoで示されている[34]。

幹細胞における重要性

高橋和利と山中伸弥によって、KLF4がマウスの胎児や成体の線維芽細胞を多能性幹細胞（iPS細胞）へ誘導するために必要な4つの因子のうちの1つ（他の3つはOct3/4、Sox2、c-Myc）であることが同定された[22]。この4つの因子はヒトの成人の線維芽細胞に対しても当てはまることが発見されている[21]。この2006年の発見以降現在に至るまで、幹細胞やその誘導に関する臨床的に重要な研究は劇的に増加した。一方で、幹細胞におけるin vivoでのKLF4の機能研究は比較的少数である。腸管幹細胞の一集団であるBmi1+幹細胞の分裂は通常は遅く、放射線照射に対する抵抗性を持ち、照射損傷後の腸管上皮の再生を担う集団であることが知られている[99]。ガンマ線照射によるDNA損傷後の腸管では、KLF4はBmi1+幹細胞の運命、そしてBmi1+幹細胞由来の細胞系統の発生を調節することで腸管の再生を調節している[36]。

出典

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000136826 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000003032 - Ensembl, May 2017
  3. ^ Human PubMed Reference:
  4. ^ Mouse PubMed Reference:
  5. ^ “Sp1 and krüppel-like factor family of transcription factors in cell growth regulation and cancer”. Journal of Cellular Physiology 188 (2): 143–60. (August 2001). doi:10.1002/jcp.1111. PMID (11424081). 
  6. ^ a b “The biology of the mammalian Krüppel-like family of transcription factors”. The International Journal of Biochemistry & Cell Biology 32 (11–12): 1103–21. (November 2000). doi:10.1016/s1357-2725(00)00059-5. PMC 2754176. PMID (11137451). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754176/. 
  7. ^ “Sp1- and Krüppel-like transcription factors”. Genome Biology 4 (2): 206. (2003). doi:10.1186/gb-2003-4-2-206. PMC 151296. PMID (12620113). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC151296/. 
  8. ^ “Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts”. Molecular Cancer 12: 89. (August 2013). doi:10.1186/1476-4598-12-89. PMC 3750599. PMID (23919723). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750599/. 
  9. ^ “Two potent nuclear localization signals in the gut-enriched Krüppel-like factor define a subfamily of closely related Krüppel proteins”. The Journal of Biological Chemistry 272 (29): 18504–7. (July 1997). doi:10.1074/jbc.272.29.18504. PMC 2268085. PMID (9218496). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268085/. 
  10. ^ a b “Entrez Gene: KLF4 Kruppel-like factor 4 (gut)”. 2022年10月16日閲覧。
  11. ^ a b “Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest”. The Journal of Biological Chemistry 271 (33): 20009–17. (August 1996). doi:10.1074/jbc.271.33.20009. PMC 2330254. PMID (8702718). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330254/. 
  12. ^ “A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells”. The Journal of Biological Chemistry 271 (49): 31384–90. (December 1996). doi:10.1074/jbc.271.49.31384. PMID (8940147). 
  13. ^ “Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction”. Nucleic Acids Research 28 (5): 1106–13. (March 2000). doi:10.1093/nar/28.5.1106. PMC 102607. PMID (10666450). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102607/. 
  14. ^ “Kruppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation”. The Journal of Biological Chemistry 282 (47): 33994–4002. (November 2007). doi:10.1074/jbc.M701847200. PMID (17908689). 
  15. ^ “Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction”. Nucleic Acids Research 28 (5): 1106–13. (March 2000). doi:10.1093/nar/28.5.1106. PMC 102607. PMID (10666450). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102607/. 
  16. ^ “The gut-enriched Krüppel-like factor suppresses the activity of the CYP1A1 promoter in an Sp1-dependent fashion”. The Journal of Biological Chemistry 273 (28): 17917–25. (July 1998). doi:10.1074/jbc.273.28.17917. PMC 2275057. PMID (9651398). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275057/. 
  17. ^ “Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elements”. The Journal of Biological Chemistry 279 (10): 8684–93. (March 2004). doi:10.1074/jbc.M308278200. PMID (14670968). 
  18. ^ a b “Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages”. The Journal of Biological Chemistry 280 (46): 38247–58. (November 2005). doi:10.1074/jbc.M509378200. PMID (16169848). 
  19. ^ “Loss of Krüppel-like factor 4 expression contributes to Sp1 overexpression and human gastric cancer development and progression”. Clinical Cancer Research 12 (21): 6395–402. (November 2006). doi:10.1158/1078-0432.CCR-06-1034. PMID (17085651). 
  20. ^ “Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells”. Science 336 (6088): 1549–54. (June 2012). Bibcode: 2012Sci...336.1549H. doi:10.1126/science.1218370. PMID (22723415). 
  21. ^ a b “Induction of pluripotent stem cells from adult human fibroblasts by defined factors”. Cell 131 (5): 861–72. (November 2007). doi:10.1016/j.cell.2007.11.019. hdl:(2433/49782). PMID (18035408). 
  22. ^ a b “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors”. Cell 126 (4): 663–76. (August 2006). doi:10.1016/j.cell.2006.07.024. hdl:(2433/159777). PMID (16904174). 
  23. ^ a b “Krüppel-like factor 4 (gut-enriched Krüppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle”. The Journal of Biological Chemistry 276 (32): 30423–8. (August 2001). doi:10.1074/jbc.M101194200. PMC 2330258. PMID (11390382). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330258/. 
  24. ^ “Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity”. Oncogene 22 (22): 3424–30. (May 2003). doi:10.1038/sj.onc.1206413. PMC 2275074. PMID (12776194). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275074/. 
  25. ^ a b c “Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage”. The Journal of Biological Chemistry 279 (6): 5035–41. (February 2004). doi:10.1074/jbc.M307631200. PMC 1262649. PMID (14627709). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1262649/. 
  26. ^ a b c “Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage”. The Journal of Biological Chemistry 278 (4): 2101–5. (January 2003). doi:10.1074/jbc.M211027200. PMC 2229830. PMID (12427745). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229830/. 
  27. ^ “Krüppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage”. Oncogene 24 (25): 4017–25. (June 2005). doi:10.1038/sj.onc.1208576. PMC 1626272. PMID (15806166). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626272/. 
  28. ^ “Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts”. Molecular Cancer 12: 89. (August 2013). doi:10.1186/1476-4598-12-89. PMC 3750599. PMID (23919723). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750599/. 
  29. ^ “Mouse embryonic fibroblasts null for the Krüppel-like factor 4 gene are genetically unstable”. Oncogene 28 (9): 1197–205. (March 2009). doi:10.1038/onc.2008.465. PMC 2667867. PMID (19137014). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667867/. 
  30. ^ “KLF4 Suppresses Tumor Formation in Genetic and Pharmacological Mouse Models of Colonic Tumorigenesis”. Molecular Cancer Research 14 (4): 385–96. (April 2016). doi:10.1158/1541-7786.MCR-15-0410. PMC 4834227. PMID (26839262). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834227/. 
  31. ^ a b c “The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene”. Nature Cell Biology 7 (11): 1074–82. (November 2005). doi:10.1038/ncb1314. hdl:(1874/17842). PMID (16244670). 
  32. ^ a b “KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells”. Cancer Biology & Therapy 4 (11): 1216–21. (November 2005). doi:10.4161/cbt.4.11.2090. PMID (16357509). 
  33. ^ a b “The diverse functions of Krüppel-like factors 4 and 5 in epithelial biology and pathobiology”. BioEssays 29 (6): 549–57. (June 2007). doi:10.1002/bies.20581. PMC 2211634. PMID (17508399). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211634/. 
  34. ^ a b c “Krüppel-like factor 4 is a radioprotective factor for the intestine following γ-radiation-induced gut injury in mice”. American Journal of Physiology. Gastrointestinal and Liver Physiology 308 (2): G121-38. (January 2015). doi:10.1152/ajpgi.00080.2014. PMC 4297857. PMID (25414097). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297857/. 
  35. ^ a b c “Krüppel-like factor 4 induces apoptosis and inhibits tumorigenic progression in SK-BR-3 breast cancer cells”. FEBS Open Bio 5: 147–54. (2 March 2015). doi:10.1016/j.fob.2015.02.003. PMC 4359971. PMID (25834779). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359971/. 
  36. ^ a b “Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice”. Stem Cell Reports 6 (6): 815–24. (June 2016). doi:10.1016/j.stemcr.2016.04.014. PMC 4911500. PMID (27237377). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911500/. 
  37. ^ “[Effect of Krüppel-like factor 4 overexpression on heat stress-induced apoptosis of Raw264.7 macrophages]”. Zhong Nan da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences 32 (6): 1002–6. (December 2007). PMID (18182717). 
  38. ^ “KLF4 promotes hydrogen-peroxide-induced apoptosis of chronic myeloid leukemia cells involving the bcl-2/bax pathway”. Cell Stress & Chaperones 15 (6): 905–12. (November 2010). doi:10.1007/s12192-010-0199-5. PMC 3024064. PMID (20401760). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024064/. 
  39. ^ “Resveratrol-induced apoptosis is mediated by early growth response-1, Krüppel-like factor 4, and activating transcription factor 3”. Cancer Prevention Research 4 (1): 116–27. (January 2011). doi:10.1158/1940-6207.CAPR-10-0218. PMC 3064282. PMID (21205742). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064282/. 
  40. ^ “The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon”. Development 129 (11): 2619–28. (June 2002). doi:10.1242/dev.129.11.2619. PMC 2225535. PMID (12015290). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225535/. 
  41. ^ “Altered expression of the KLF4 in colorectal cancers”. Pathology, Research and Practice 202 (8): 585–9. (2006). doi:10.1016/j.prp.2006.05.001. PMID (16814484). 
  42. ^ “Haploinsufficiency of Krüppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis”. Cancer Research 67 (15): 7147–54. (August 2007). doi:10.1158/0008-5472.CAN-07-1302. PMC 2373271. PMID (17671182). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373271/. 
  43. ^ a b “Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Krüppel-like factor 4 gene”. Developmental Biology 349 (2): 310–20. (January 2011). doi:10.1016/j.ydbio.2010.11.001. PMC 3022386. PMID (21070761). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022386/. 
  44. ^ “Postnatal gene expression in the normal mouse cornea by SAGE”. Investigative Ophthalmology & Visual Science 45 (2): 429–40. (February 2004). doi:10.1167/iovs.03-0449. PMID (14744882). 
  45. ^ “Regulation of corneal epithelial barrier function by Kruppel-like transcription factor 4”. Investigative Ophthalmology & Visual Science 52 (3): 1762–9. (March 2011). doi:10.1167/iovs.10-6134. PMC 3101671. PMID (21051695). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101671/. 
  46. ^ “Identification of candidate Klf4 target genes reveals the molecular basis of the diverse regulatory roles of Klf4 in the mouse cornea”. Investigative Ophthalmology & Visual Science 49 (8): 3360–70. (August 2008). doi:10.1167/iovs.08-1811. PMC 2774783. PMID (18469187). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774783/. 
  47. ^ “Klf4 is a transcription factor required for establishing the barrier function of the skin”. Nature Genetics 22 (4): 356–60. (August 1999). doi:10.1038/11926. PMID (10431239). 
  48. ^ “Ectopic expression of kruppel like factor 4 (Klf4) accelerates formation of the epidermal permeability barrier”. Development 130 (12): 2767–77. (June 2003). doi:10.1242/dev.00477. PMID (12736219). 
  49. ^ “Deficiency of the Kruppel-like factor KLF4 correlates with increased cell proliferation and enhanced skin tumorigenesis”. Carcinogenesis 33 (6): 1239–46. (June 2012). doi:10.1093/carcin/bgs143. PMC 3388492. PMID (22491752). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388492/. 
  50. ^ “Krüppel-like factor 4 regulates membranous and endochondral ossification”. Experimental Cell Research 318 (4): 311–25. (February 2012). doi:10.1016/j.yexcr.2011.12.013. PMID (22206865). 
  51. ^ “Kruppel-like factor 4 expression in osteoblasts represses osteoblast-dependent osteoclast maturation”. Cell and Tissue Research 358 (1): 177–87. (October 2014). doi:10.1007/s00441-014-1931-8. PMID (24927920). 
  52. ^ “Kruppel-like factor 4 attenuates osteoblast formation, function, and cross talk with osteoclasts”. The Journal of Cell Biology 204 (6): 1063–74. (March 2014). doi:10.1083/jcb.201308102. PMC 3998795. PMID (24616223). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998795/. 
  53. ^ “Spatial and temporal expression of KLF4 and KLF5 during murine tooth development”. Archives of Oral Biology 54 (5): 403–11. (May 2009). doi:10.1016/j.archoralbio.2009.02.003. PMID (19268913). 
  54. ^ “Krüppel-like factor 4 is widely expressed in the mouse male and female reproductive tract and responds as an immediate early gene to activation of the protein kinase A in TM4 Sertoli cells”. Reproduction 139 (4): 771–82. (April 2010). doi:10.1530/REP-09-0531. PMID (20051481). 
  55. ^ “Developmental and cell type-specific expression of the zinc finger transcription factor Krüppel-like factor 4 (Klf4) in postnatal mouse testis”. Mechanisms of Development 115 (1–2): 167–9. (July 2002). doi:10.1016/s0925-4773(02)00127-2. PMID (12049784). 
  56. ^ “Expression of CLMP, a novel tight junction protein, is mediated via the interaction of GATA with the Kruppel family proteins, KLF4 and Sp1, in mouse TM4 Sertoli cells”. Journal of Cellular Physiology 214 (2): 334–44. (February 2008). doi:10.1002/jcp.21201. PMID (17620326). 
  57. ^ “Krüppel-like factor 4 is involved in functional differentiation of testicular Sertoli cells”. Developmental Biology 315 (2): 552–66. (March 2008). doi:10.1016/j.ydbio.2007.12.018. PMC 2292099. PMID (18243172). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292099/. 
  58. ^ a b “Kruppel-like factor 4 regulates endothelial inflammation”. The Journal of Biological Chemistry 282 (18): 13769–79. (May 2007). doi:10.1074/jbc.M700078200. PMID (17339326). 
  59. ^ “Kruppel-like factor-4 transcriptionally regulates VE-cadherin expression and endothelial barrier function”. Circulation Research 107 (8): 959–66. (October 2010). doi:10.1161/CIRCRESAHA.110.219592. PMC 3018700. PMID (20724706). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018700/. 
  60. ^ “A functional screen for Krüppel-like factors that regulate the human gamma-globin gene through the CACCC promoter element”. Blood Cells, Molecules & Diseases 35 (2): 227–35. (2005). doi:10.1016/j.bcmd.2005.04.009. PMID (16023392). 
  61. ^ “KLF4 regulates the expression of interleukin-10 in RAW264.7 macrophages”. Biochemical and Biophysical Research Communications 362 (3): 575–81. (October 2007). doi:10.1016/j.bbrc.2007.07.157. PMID (17719562). 
  62. ^ “The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation”. The EMBO Journal 26 (18): 4138–48. (September 2007). doi:10.1038/sj.emboj.7601824. PMC 2230668. PMID (17762869). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230668/. 
  63. ^ a b “Krüppel-like factor 4 regulates B cell number and activation-induced B cell proliferation”. Journal of Immunology 179 (7): 4679–84. (October 2007). doi:10.4049/jimmunol.179.7.4679. PMC 2262926. PMID (17878366). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262926/. 
  64. ^ “KLF4 is a FOXO target gene that suppresses B cell proliferation”. International Immunology 20 (5): 671–81. (May 2008). doi:10.1093/intimm/dxn024. PMID (18375530). 
  65. ^ “Generation of induced pluripotent stem cells from human kidney mesangial cells”. Journal of the American Society of Nephrology 22 (7): 1213–20. (July 2011). doi:10.1681/ASN.2010101022. PMC 3137569. PMID (21566060). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137569/. 
  66. ^ “Renin-angiotensin blockade resets podocyte epigenome through Kruppel-like Factor 4 and attenuates proteinuria”. Kidney International 88 (4): 745–53. (October 2015). doi:10.1038/ki.2015.178. PMID (26108068). 
  67. ^ “The role of Krüppel-like factor 4 in transforming growth factor-β-induced inflammatory and fibrotic responses in human proximal tubule cells”. Clinical and Experimental Pharmacology & Physiology 42 (6): 680–6. (June 2015). doi:10.1111/1440-1681.12405. PMID (25882815). 
  68. ^ “Matrix-Stiffness-Regulated Inverse Expression of Krüppel-Like Factor 5 and Krüppel-Like Factor 4 in the Pathogenesis of Renal Fibrosis”. The American Journal of Pathology 185 (9): 2468–81. (September 2015). doi:10.1016/j.ajpath.2015.05.019. PMID (26212907). 
  69. ^ “Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer”. Oncogene 23 (2): 395–402. (January 2004). doi:10.1038/sj.onc.1207067. PMC 1351029. PMID (14724568). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1351029/. 
  70. ^ “Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression”. Cancer Research 65 (7): 2746–54. (April 2005). doi:10.1158/0008-5472.CAN-04-3619. PMID (15805274). 
  71. ^ “Expression of the gut-enriched Krüppel-like factor gene during development and intestinal tumorigenesis”. FEBS Letters 419 (2–3): 239–43. (December 1997). doi:10.1016/s0014-5793(97)01465-8. PMC 2330259. PMID (9428642). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330259/. 
  72. ^ “Epigenetics of prostate cancer: beyond DNA methylation”. Journal of Cellular and Molecular Medicine 10 (1): 100–25. (January 2006). doi:10.1111/j.1582-4934.2006.tb00293.x. PMC 3933104. PMID (16563224). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933104/. 
  73. ^ “Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer”. Biochemical and Biophysical Research Communications 308 (2): 251–6. (August 2003). doi:10.1016/s0006-291x(03)01356-1. PMID (12901861). 
  74. ^ “Putative tumor-suppressive function of Kruppel-like factor 4 in primary lung carcinoma”. Clinical Cancer Research 15 (18): 5688–95. (September 2009). doi:10.1158/1078-0432.CCR-09-0310. PMC 2745510. PMID (19737957). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745510/. 
  75. ^ “Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF”. Cell Growth & Differentiation 10 (6): 423–34. (June 1999). PMID (10392904). 
  76. ^ “Increase of GKLF messenger RNA and protein expression during progression of breast cancer”. Cancer Research 60 (22): 6488–95. (November 2000). PMID (11103818). 
  77. ^ “Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia”. Oncogene 24 (9): 1491–500. (February 2005). doi:10.1038/sj.onc.1208307. PMC 1361530. PMID (15674344). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361530/. 
  78. ^ “KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia”. Cancer Biology & Therapy 4 (12): 1401–8. (December 2005). doi:10.4161/cbt.4.12.2355. PMC 1361751. PMID (16357510). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361751/. 
  79. ^ a b “Klf4 overexpression activates epithelial cytokines and inflammation-mediated esophageal squamous cell cancer in mice”. Gastroenterology 139 (6): 2124–2134.e9. (December 2010). doi:10.1053/j.gastro.2010.08.048. PMC 3457785. PMID (20816834). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457785/. 
  80. ^ “p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells”. Cell Cycle 10 (8): 1312–21. (April 2011). doi:10.4161/cc.10.8.15363. PMID (21490434). 
  81. ^ “DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer”. PLOS ONE 8 (9): e73940. (9 September 2013). Bibcode: 2013PLoSO...873940S. doi:10.1371/journal.pone.0073940. PMC 3767662. PMID (24040120). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767662/. 
  82. ^ “The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs”. Nature Cell Biology 11 (12): 1487–95. (December 2009). doi:10.1038/ncb1998. PMID (19935649). 
  83. ^ “Doxycycline inducible Krüppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells”. PLOS ONE 9 (8): e105331. (19 August 2014). Bibcode: 2014PLoSO...9j5331C. doi:10.1371/journal.pone.0105331. PMC 4138168. PMID (25137052). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138168/. 
  84. ^ “MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1”. Molecular Cancer 10: 99. (August 2011). doi:10.1186/1476-4598-10-99. PMC 3173388. PMID (21851624). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173388/. 
  85. ^ “Aldehyde dehydrogenase 1, a functional marker for identifying cancer stem cells in human nasopharyngeal carcinoma”. Cancer Letters 330 (2): 181–9. (April 2013). doi:10.1016/j.canlet.2012.11.046. PMID (23220285). 
  86. ^ “Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR‑145”. International Journal of Oncology 42 (4): 1473–81. (April 2013). doi:10.3892/ijo.2013.1825. PMID (23404342). 
  87. ^ “NF-κB regulates mesenchymal transition for the induction of non-small cell lung cancer initiating cells”. PLOS ONE 8 (7): e68597. (2013). Bibcode: 2013PLoSO...868597K. doi:10.1371/journal.pone.0068597. PMC 3728367. PMID (23935876). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728367/. 
  88. ^ “Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor β-initiated prostate cancer epithelial-mesenchymal transition”. Molecular and Cellular Biology 32 (5): 941–53. (March 2012). doi:10.1128/MCB.06306-11. PMC 3295188. PMID (22203039). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295188/. 
  89. ^ “microRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30 expression and promoting EGF and TGF-β actions”. Oncogene 33 (38): 4664–74. (September 2014). doi:10.1038/onc.2013.405. PMC 3979498. PMID (24096486). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979498/. 
  90. ^ “SNAI2 controls the undifferentiated state of human epidermal progenitor cells”. Stem Cells 32 (12): 3209–18. (December 2014). doi:10.1002/stem.1809. PMC 4339269. PMID (25100569). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339269/. 
  91. ^ “Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Lung Cancer Cells and Inhibits Regulating Epithelial-to-Mesenchymal Transition”. Oncology Research 24 (2): 81–7. (2016). doi:10.3727/096504016X14597766487717. PMC 7838665. PMID (27296948). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838665/. 
  92. ^ “MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/Notch1/E-cadherin in cisplatin-resistant nasopharyngeal carcinoma cells”. American Journal of Cancer Research 6 (2): 141–56. (15 January 2016). PMC 4859649. PMID (27186392). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859649/. 
  93. ^ “Krüppel-like factor 4 regulates macrophage polarization”. The Journal of Clinical Investigation 121 (7): 2736–49. (July 2011). doi:10.1172/JCI45444. PMC 3223832. PMID (21670502). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223832/. 
  94. ^ “Myeloid Krüppel-like factor 4 deficiency augments atherogenesis in ApoE-/- mice--brief report”. Arteriosclerosis, Thrombosis, and Vascular Biology 32 (12): 2836–8. (December 2012). doi:10.1161/ATVBAHA.112.300471. PMC 3574634. PMID (23065827). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574634/. 
  95. ^ a b “Krüppel-like factor 4 synergizes with CREB to increase the activity of apolipoprotein E gene promoter in macrophages”. Biochemical and Biophysical Research Communications 468 (1–2): 66–72. (December 2015). doi:10.1016/j.bbrc.2015.10.163. PMID (26546821). 
  96. ^ “HIV vasculopathy: role of mononuclear cell-associated Krüppel-like factors 2 and 4”. AIDS 29 (13): 1643–50. (August 2015). doi:10.1097/QAD.0000000000000756. PMC 4571286. PMID (26372274). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571286/. 
  97. ^ “KLF4 is a key determinant in the development and progression of cerebral cavernous malformations”. EMBO Molecular Medicine 8 (1): 6–24. (November 2015). doi:10.15252/emmm.201505433. PMC 4718159. PMID (26612856). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718159/. 
  98. ^ “Genetic deletion of Klf4 in the mouse intestinal epithelium ameliorates dextran sodium sulfate-induced colitis by modulating the NF-κB pathway inflammatory response”. Inflammatory Bowel Diseases 20 (5): 811–20. (May 2014). doi:10.1097/MIB.0000000000000022. PMC 4091934. PMID (24681655). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091934/. 
  99. ^ “The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations”. Proceedings of the National Academy of Sciences of the United States of America 109 (2): 466–71. (January 2012). Bibcode: 2012PNAS..109..466Y. doi:10.1073/pnas.1118857109. PMC 3258636. PMID (22190486). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258636/. 

関連文献

  • “KLF4, p21 and context-dependent opposing forces in cancer”. Nature Reviews. Cancer 6 (1): 11–23. (January 2006). doi:10.1038/nrc1780. PMID (16372018). 
  • “Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest”. The Journal of Biological Chemistry 271 (33): 20009–17. (August 1996). doi:10.1074/jbc.271.33.20009. PMC 2330254. PMID (8702718). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330254/. 
  • “A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells”. The Journal of Biological Chemistry 271 (49): 31384–90. (December 1996). doi:10.1074/jbc.271.49.31384. PMID (8940147). 
  • “Human EZF, a Krüppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains”. The Journal of Biological Chemistry 273 (2): 1026–31. (January 1998). doi:10.1074/jbc.273.2.1026. PMID (9422764). 
  • “The gut-enriched Krüppel-like factor suppresses the activity of the CYP1A1 promoter in an Sp1-dependent fashion”. The Journal of Biological Chemistry 273 (28): 17917–25. (July 1998). doi:10.1074/jbc.273.28.17917. PMC 2275057. PMID (9651398). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275057/. 
  • “Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF”. Cell Growth & Differentiation 10 (6): 423–34. (June 1999). PMID (10392904). 
  • “Klf4 is a transcription factor required for establishing the barrier function of the skin”. Nature Genetics 22 (4): 356–60. (August 1999). doi:10.1038/11926. PMID (10431239). 
  • “Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction”. Nucleic Acids Research 28 (5): 1106–13. (March 2000). doi:10.1093/nar/28.5.1106. PMC 102607. PMID (10666450). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102607/. 
  • “The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter”. The Journal of Biological Chemistry 275 (24): 18391–8. (June 2000). doi:10.1074/jbc.C000062200. PMC 2231805. PMID (10749849). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231805/. 
  • “The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact”. FEBS Letters 473 (1): 95–100. (May 2000). doi:10.1016/S0014-5793(00)01468-X. PMID (10802067). 
  • “Synergistic activation of the rat laminin gamma1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1”. Nucleic Acids Research 30 (11): 2270–9. (June 2002). doi:10.1093/nar/30.11.2270. PMC 117209. PMID (12034813). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC117209/. 
  • “Gut-enriched Kruppel-like factor represses ornithine decarboxylase gene expression and functions as checkpoint regulator in colonic cancer cells”. The Journal of Biological Chemistry 277 (48): 46831–9. (November 2002). doi:10.1074/jbc.M204816200. PMID (12297499). 
  • “Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage”. The Journal of Biological Chemistry 278 (4): 2101–5. (January 2003). doi:10.1074/jbc.M211027200. PMC 2229830. PMID (12427745). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229830/. 
  • “Down-regulation of gut-enriched Kruppel-like factor expression in esophageal cancer”. World Journal of Gastroenterology 8 (6): 966–70. (December 2002). doi:10.3748/wjg.v8.i6.966. PMC 4656400. PMID (12439907). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656400/. 
  • “Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation”. Journal of Molecular Biology 326 (3): 665–77. (February 2003). doi:10.1016/S0022-2836(02)01449-3. PMC 2693487. PMID (12581631). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693487/. 
  • “Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity”. Oncogene 22 (22): 3424–30. (May 2003). doi:10.1038/sj.onc.1206413. PMC 2275074. PMID (12776194). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275074/. 
  • “Transcriptional regulation of A33 antigen expression by gut-enriched Krüppel-like factor”. Oncogene 22 (28): 4434–43. (July 2003). doi:10.1038/sj.onc.1206508. PMID (12853980). 
  • “Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer”. Biochemical and Biophysical Research Communications 308 (2): 251–6. (August 2003). doi:10.1016/S0006-291X(03)01356-1. PMID (12901861). 
  • “Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor”. American Journal of Physiology. Gastrointestinal and Liver Physiology 286 (1): G23-30. (January 2004). doi:10.1152/ajpgi.00203.2003. PMID (12919939). 

関連項目

  • (KLFファミリー)（英語版）

外部リンク

ウィキペディア、ウィキ、本、library、論文、読んだ、ダウンロード、自由、無料ダウンロード、mp3、video、mp4、3gp、 jpg、jpeg、gif、png、画像、音楽、歌、映画、本、ゲーム、ゲーム。