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Title: Klf4  
Author: World Heritage Encyclopedia
Language: English
Subject: SOX2, KLF3, Telomerase reverse transcriptase, Induced stem cells, Shinya Yamanaka
Collection: Transcription Factors
Publisher: World Heritage Encyclopedia


Kruppel-like factor 4 (gut)
Symbols  ; EZF; GKLF
External IDs GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Kruppel-like factor 4 (KLF4) is a member of the KLF family of transcription factors and regulates proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer.[1]

In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).

In humans, the protein is encoded by the KLF4 gene.[2] The KLF4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.[3]


  • Interactions 1
  • See also 2
  • References 3
  • Further reading 4
  • External links 5


KLF4 has been shown to interact with CREB-binding protein.[4]

It was found that the transcription factor Klf4 present at the promoter of an enzymatic subunit of telomerase (TERT), where it formed a complex with β-catenin. Klf4 was required for accumulation of β-catenin at the Tert promoter but was unable to stimulate Tert expression in the absence of β-catenin.[5]

See also


  1. ^ El-Karim et al. (2013). "Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts". Molecular Cancer.  
  2. ^ "Entrez Gene: KLF4 Kruppel-like factor 4 (gut)". 
  3. ^ "Kruppel-like factor 4". 
  4. ^ Geiman DE, Ton-That H, Johnson JM, Yang VW (March 2000). "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 Res. 28 (5): 1106–13.  
  5. ^ Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, Hein K, Vogt R, Kemler R (June 2012). "Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells". Science 336 (6088): 1549–54.  

Further reading

  • Rowland BD, Peeper DS (2006). "KLF4, p21 and context-dependent opposing forces in cancer.". Nat. Rev. Cancer 6 (1): 11–23.  
  • Shields JM, Christy RJ, Yang VW (1996). "Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.". J. Biol. Chem. 271 (33): 20009–17.  
  • Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B (1997). "A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.". J. Biol. Chem. 271 (49): 31384–90.  
  • Yet SF, McA'Nulty MM, Folta SC, et al. (1998). "Human EZF, a Krüppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.". J. Biol. Chem. 273 (2): 1026–31.  
  • Zhang W, Shields JM, Sogawa K, et al. (1998). "The gut-enriched Krüppel-like factor suppresses the activity of the CYP1A1 promoter in an Sp1-dependent fashion.". J. Biol. Chem. 273 (28): 17917–25.  
  • Foster KW, Ren S, Louro ID, et al. (1999). "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 Differ. 10 (6): 423–34.  
  • Segre JA, Bauer C, Fuchs E (1999). "Klf4 is a transcription factor required for establishing the barrier function of the skin.". Nat. Genet. 22 (4): 356–60.  
  • Geiman DE, Ton-That H, Johnson JM, Yang VW (2000). "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 Res. 28 (5): 1106–13.  
  • Zhang W, Geiman DE, Shields JM, et al. (2000). "The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.". J. Biol. Chem. 275 (24): 18391–8.  
  • Okano J, Opitz OG, Nakagawa H, et al. (2000). "The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact.". FEBS Lett. 473 (1): 95–100.  
  • Higaki Y, Schullery D, Kawata Y, et al. (2002). "Synergistic activation of the rat laminin gamma1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1.". Nucleic Acids Res. 30 (11): 2270–9.  
  • Chen ZY, Shie JL, Tseng CC (2003). "Gut-enriched Kruppel-like factor represses ornithine decarboxylase gene expression and functions as checkpoint regulator in colonic cancer cells.". J. Biol. Chem. 277 (48): 46831–9.  
  • Yoon HS, Chen X, Yang VW (2003). "Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage.". J. Biol. Chem. 278 (4): 2101–5.  
  • Wang N, Liu ZH, Ding F, et al. (2003). "Down-regulation of gut-enriched Kruppel-like factor expression in esophageal cancer.". World J. Gastroenterol. 8 (6): 966–70.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903.  
  • Chen X, Whitney EM, Gao SY, Yang VW (2003). "Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.". J. Mol. Biol. 326 (3): 665–77.  
  • Dang DT, Chen X, Feng J, et al. (2003). "Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity.". Oncogene 22 (22): 3424–30.  
  • Mao Z, Song S, Zhu Y, et al. (2003). "Transcriptional regulation of A33 antigen expression by gut-enriched Krüppel-like factor.". Oncogene 22 (28): 4434–43.  
  • Ohnishi S, Ohnami S, Laub F, et al. (2003). "Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer.". Biochem. Biophys. Res. Commun. 308 (2): 251–6.  
  • Hinnebusch BF, Siddique A, Henderson JW, et al. (2004). "Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor.". Am. J. Physiol. Gastrointest. Liver Physiol. 286 (1): G23–30.  

External links

  • KLF4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
  • KLF4 microarray expression results and literature

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