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Gene Review

KLF4  -  Kruppel-like factor 4 (gut)

Homo sapiens

Synonyms: EZF, Epithelial zinc finger protein EZF, GKLF, Gut-enriched krueppel-like factor, Krueppel-like factor 4
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Disease relevance of KLF4


High impact information on KLF4


Biological context of KLF4

  • The present study examines the requirement of KLF4 in mediating the p53-dependent cell cycle arrest process in response to DNA damage [9].
  • We present evidence for an equally important role of KLF4 in maintaining the integrity of the G2/M checkpoint following DNA damage [1].
  • Taken together, these results indicate that KLF4 can act to repress HDC gene expression by Sp1-dependent and -independent mechanisms [10].
  • The mechanism of action of KLF4 does not involve apoptosis [2].
  • We find that KLF4 overexpression reduces colony formation, cell migration and invasion, and in vivo tumorigenecity [2].

Anatomical context of KLF4

  • When KLF4 was inhibited by small interfering RNA, irradiated HCT116 cells exhibited increased mitotic indices and a rise in cyclin B1 levels [1].
  • Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor, the expression of which is enriched in the postmitotic cells of the intestinal epithelium [2].
  • Co-transfection of Zf9 and GKLF/KLF4, which is also a member of the Krüppel-like factors and expressed in the esophageal squamous epithelium, leads to coactivation in an additive fashion [11].
  • The present study was undertaken to examine the role of KLF4 in the butyrate-mediated effect in colon cancer HT-29 cells [12].
  • We then transduced the KLF4 and KLF5 genes into the bladder cancer cell lines using adenoviral vectors to examine the biological activities of the genes on those cells [13].

Associations of KLF4 with chemical compounds


Physical interactions of KLF4


Regulatory relationships of KLF4

  • We show that wild-type CDX2 activates the GKLF promoter and that the mutated CDX2 has a dominant negative effect on wild-type function [3].
  • Co-transfection experiments showed that KLF4 repressed the cyclin B1 promoter through a specific GC-rich element [1].
  • Conversely, in a HCT116 p53+/+ cell line stably transfected with small hairpin RNA (shRNA) designed to specifically inhibit KLF4, gamma-irradiation induced centrosome amplification [21].
  • Cotransfection experiments showed that KLF4 overexpression suppressed the promoter activity of the cyclin E gene [21].
  • Furthermore, KLF4 regulates expression of a group of epithelial-specific keratin genes in a manner consistent with a potential locus control region function [22].

Other interactions of KLF4

  • Overexpression of HDAC1 significantly attenuated transcriptional activation of the KLF4 promoter by butyrate or TSA [12].
  • Furthermore, we demonstrate that there is a physical interaction between GKLF and Zf9, a novel finding for Krüppel-like family members [11].
  • Therefore, in this report we studied the involvement of the KLF4 and KLF5 genes in bladder carcinogenesis [13].
  • In each case, Cdc2 kinase measurements showed an inverse correlation between Cdc2 kinase activities and KLF4 levels [1].
  • In each case the increase or decrease in KLF4 level because of conditional induction or siRNA inhibition, respectively, was accompanied by an increase or decrease in the level of p21(WAF1/CIP1) [9].

Analytical, diagnostic and therapeutic context of KLF4


  1. Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage. Yoon, H.S., Yang, V.W. J. Biol. Chem. (2004) [Pubmed]
  2. Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity. Dang, D.T., Chen, X., Feng, J., Torbenson, M., Dang, L.H., Yang, V.W. Oncogene (2003) [Pubmed]
  3. Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2. Dang, D.T., Mahatan, C.S., Dang, L.H., Agboola, I.A., Yang, V.W. Oncogene (2001) [Pubmed]
  4. Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression. Wei, D., Gong, W., Kanai, M., Schlunk, C., Wang, L., Yao, J.C., Wu, T.T., Huang, S., Xie, K. Cancer Res. (2005) [Pubmed]
  5. Putative tumor-suppressive function of Kruppel-like factor 4 in primary lung carcinoma. Hu, W., Hofstetter, W.L., Li, H., Zhou, Y., He, Y., Pataer, A., Wang, L., Xie, K., Swisher, S.G., Fang, B. Clin. Cancer Res. (2009) [Pubmed]
  6. Klf4 is a transcription factor required for establishing the barrier function of the skin. Segre, J.A., Bauer, C., Fuchs, E. Nat. Genet. (1999) [Pubmed]
  7. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Katz, J.P., Perreault, N., Goldstein, B.G., Actman, L., McNally, S.R., Silberg, D.G., Furth, E.E., Kaestner, K.H. Gastroenterology (2005) [Pubmed]
  8. The keratin 19 promoter is potent for cell-specific targeting of genes in transgenic mice. Brembeck, F.H., Moffett, J., Wang, T.C., Rustgi, A.K. Gastroenterology (2001) [Pubmed]
  9. Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage. Yoon, H.S., Chen, X., Yang, V.W. J. Biol. Chem. (2003) [Pubmed]
  10. Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elements. Ai, W., Liu, Y., Langlois, M., Wang, T.C. J. Biol. Chem. (2004) [Pubmed]
  11. The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact. Okano, J., Opitz, O.G., Nakagawa, H., Jenkins, T.D., Friedman, S.L., Rustgi, A.K. FEBS Lett. (2000) [Pubmed]
  12. Krüppel-like factor 4 is transactivated by butyrate in colon cancer cells. Chen, Z.Y., Rex, S., Tseng, C.C. J. Nutr. (2004) [Pubmed]
  13. Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer. Ohnishi, S., Ohnami, S., Laub, F., Aoki, K., Suzuki, K., Kanai, Y., Haga, K., Asaka, M., Ramirez, F., Yoshida, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  14. Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1. Blanchon, L., Nores, R., Gallot, D., Marceau, G., Borel, V., Yang, V.W., Bocco, J.L., Lémery, D., Panzetta-Dutari, G., Sapin, V. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. The Kruppel-like KLF4 transcription factor, a novel regulator of urokinase receptor expression, drives synthesis of this binding site in colonic crypt luminal surface epithelial cells. Wang, H., Yang, L., Jamaluddin, M.S., Boyd, D.D. J. Biol. Chem. (2004) [Pubmed]
  16. The leukocyte integrin gene CD11d is repressed by gut-enriched Kruppel-like factor 4 in myeloid cells. Noti, J.D., Johnson, A.K., Dillon, J.D. J. Biol. Chem. (2005) [Pubmed]
  17. Destabilization of Krüppel-like factor 4 protein in response to serum stimulation involves the ubiquitin-proteasome pathway. Chen, Z.Y., Wang, X., Zhou, Y., Offner, G., Tseng, C.C. Cancer Res. (2005) [Pubmed]
  18. STAT1 is required for IFN-gamma-mediated gut-enriched Krüppel-like factor expression. Chen, Z.Y., Shie, J.L., Tseng, C.C. Exp. Cell Res. (2002) [Pubmed]
  19. Gut-enriched kruppel-like factor interaction with smad3 inhibits myofibroblast differentiation. Hu, B., Wu, Z., Liu, T., Ullenbruch, M.R., Jin, H., Phan, S.H. Am. J. Respir. Cell Mol. Biol. (2007) [Pubmed]
  20. 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. Geiman, D.E., Ton-That, H., Johnson, J.M., Yang, V.W. Nucleic Acids Res. (2000) [Pubmed]
  21. Krüppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage. Yoon, H.S., Ghaleb, A.M., Nandan, M.O., Hisamuddin, I.M., Dalton, W.B., Yang, V.W. Oncogene (2005) [Pubmed]
  22. Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation. Chen, X., Whitney, E.M., Gao, S.Y., Yang, V.W. J. Mol. Biol. (2003) [Pubmed]
  23. Cell and tissue specific expression of human Krüppel-like transcription factors in human ocular surface. Chiambaretta, F., De Graeve, F., Turet, G., Marceau, G., Gain, P., Dastugue, B., Rigal, D., Sapin, V. Mol. Vis. (2004) [Pubmed]
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