Genomes and Genes
Gene Symbol: GKLF
Description: Kruppel like factor 4
Alias: GKLF, Krueppel-like factor 4, Kruppel-like factor 4 (gut)
- Wassmann S, Wassmann K, Jung A, Velten M, Knuefermann P, Petoumenos V, et al. Induction of p53 by GKLF is essential for inhibition of proliferation of vascular smooth muscle cells. J Mol Cell Cardiol. 2007;43:301-7 pubmed..Recent studies have demonstrated that the transcription factor gut-enriched Krüppel-like factor (GKLF, KLF4) is involved in redox-sensitive growth arrest of VSMC...
- Zeng Q, Wei B, Zhao Y, Wang X, Fu Q, Liu H, et al. Shh mediates PDGF-induced contractile-to-synthetic phenotypic modulation in vascular smooth muscle cells through regulation of KLF4. Exp Cell Res. 2016;345:82-92 pubmed publisher..Taken together, the results provide critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4. ..
- Fujii Y, Kakegawa M, Koide H, Akagi T, Yokota T. Zfp296 is a novel Klf4-interacting protein and functions as a negative regulator. Biochem Biophys Res Commun. 2013;441:411-7 pubmed publisher..In contrast, a reporter assay showed that the Lefty1 promoter was activated by Klf4, and that the enhanced activity was repressed by Zfp296. These findings suggest that Zfp296 is a functional regulator of Klf4 in ES cells. ..
- Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, et al. Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol. 2006;26:7772-82 pubmed..DNA microarray analysis revealed that a subset of putative Oct3/4 target genes may be regulated in the same manner. Our findings shed light on a novel function of Oct3/4 in ES cells. ..
- Mun G, Boo Y. A regulatory role of Kruppel-like factor 4 in endothelial argininosuccinate synthetase 1 expression in response to laminar shear stress. Biochem Biophys Res Commun. 2012;420:450-5 pubmed publisher..The ectopic expression of KLF4 led to the increase of ASS1 expression and NO production. The present study demonstrated a key regulatory role of KLF4 in the endothelial ASS1 expression and NO production in response to LSS. ..
- Zhang X, Zheng B, Gu C, Fu J, Wen J. TGF-?1 downregulates AT1 receptor expression via PKC-?-mediated Sp1 dissociation from KLF4 and Smad-mediated PPAR-? association with KLF4. Arterioscler Thromb Vasc Biol. 2012;32:1015-23 pubmed publisher..On activation of TGF-? signaling, KLF4 mediates Sp1 dissociation from, and PPAR-? association with, the AT1R promoter, leading to downregulation of AT1R expression in VSMCs. ..
- Hamil K, Hall S. Cloning of rat Sertoli cell follicle-stimulating hormone primary response complementary deoxyribonucleic acid: regulation of TSC-22 gene expression. Endocrinology. 1994;134:1205-12 pubmed..A 5-kb transcript became detectable by 30 days and decreased after 50 days of age. Ovarian 1.8-kb TSC-22 transcript levels increased about 2-fold during the same maturation period. ..
- He M, Zheng B, Zhang Y, Zhang X, Wang C, Yang Z, et al. KLF4 mediates the link between TGF-Î²1-induced gene transcription and H3 acetylation in vascular smooth muscle cells. FASEB J. 2015;29:4059-70 pubmed publisher..Taken together, the results of our study reveal a novel mechanism whereby KLF4 mediates the link between TGF-Î²1-induced gene transcription activation and H3 acetylation during VSMC differentiation. ..
- Yoshida T, Gan Q, Owens G. Kruppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. Am J Physiol Cell Physiol. 2008;295:C1175-82 pubmed publisher..Coimmunoprecipitation assays showed that Klf4 interacted with HDAC5. Results provide evidence that Klf4, Elk-1, and HDACs coordinately mediate POVPC-induced suppression of SMC differentiation marker genes. ..
- Yet S, McA Nulty M, Folta S, Yen H, Yoshizumi M, Hsieh C, et al. Human EZF, a Krüppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains. J Biol Chem. 1998;273:1026-31 pubmed..Sequence analysis indicated that our clone, hEZF, is the human homologue of the recently reported mouse EZF and GKLF. hEZF is a single-copy gene that maps to chromosome 9q31...
- Qin S, Zou Y, Zhang C. Cross-talk between KLF4 and STAT3 regulates axon regeneration. Nat Commun. 2013;4:2633 pubmed publisher..These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS. ..
- Ohnesorge N, Viemann D, Schmidt N, Czymai T, Spiering D, Schmolke M, et al. Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4). J Biol Chem. 2010;285:26199-210 pubmed publisher..Our data underscore a major protective function of the MEK5/Erk5/KLF4 module in ECs and implicate agonistic Erk5 activation as potential strategy for treatment of vascular diseases. ..
- Li J, Zheng H, Yu F, Yu T, Liu C, Huang S, et al. Deficiency of the Kruppel-like factor KLF4 correlates with increased cell proliferation and enhanced skin tumorigenesis. Carcinogenesis. 2012;33:1239-46 pubmed publisher..Taken together, our data suggest that KLF4 inhibits cell proliferation, migration and adhesion and that loss of KLF4 promotes skin tumorigenesis. ..
- Ge S, Zhang L, Xie J, Liu F, He J, He J, et al. MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4. Ann Hepatol. 2016;15:918-928 pubmed..Thus, targeted transfer of miR-146b into HSCs could be a useful strategy for the treatment of hepatic fibrosis. ..
- Liao X, Zhang R, Lu Y, Prosdocimo D, Sangwung P, Zhang L, et al. Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis. J Clin Invest. 2015;125:3461-76 pubmed publisher..Collectively, these findings identify KLF4 as a nodal transcriptional regulator of mitochondrial homeostasis. ..
- Li H, Han M, Bernier M, Zheng B, Sun S, Su M, et al. Krüppel-like factor 4 promotes differentiation by transforming growth factor-beta receptor-mediated Smad and p38 MAPK signaling in vascular smooth muscle cells. J Biol Chem. 2010;285:17846-56 pubmed publisher..This study demonstrates a novel mechanism by which TGF-beta1 regulates VSMC differentiation. ..
- Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, et al. Wnt/?-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 2012;336:1549-54 pubmed publisher..We uncover a previously unknown link between the stem cell and oncogenic potential whereby ?-catenin regulates Tert expression, and thereby telomere length, which could be critical in human regenerative therapy and cancer. ..
- Kunarso G, Wong K, Stanton L, Lipovich L. Detailed characterization of the mouse embryonic stem cell transcriptome reveals novel genes and intergenic splicing associated with pluripotency. BMC Genomics. 2008;9:155 pubmed publisher..RNAi results indicate that, despite their strong association with pluripotency, these five transcriptomic novelties may not be required for maintaining it. ..
- Deaton R, Gan Q, Owens G. Sp1-dependent activation of KLF4 is required for PDGF-BB-induced phenotypic modulation of smooth muscle. Am J Physiol Heart Circ Physiol. 2009;296:H1027-37 pubmed publisher..Taken together, the results suggest a novel role for Sp1 in increasing the expression of KLF4 in phenotypically modulated SMCs. ..
- Liu Y, Sinha S, Owens G. A transforming growth factor-beta control element required for SM alpha-actin expression in vivo also partially mediates GKLF-dependent transcriptional repression. J Biol Chem. 2003;278:48004-11 pubmed..in transgenic mice and 2) further characterize the possible role and mechanisms by which the TCE-binding factor GKLF/KLF4 induces repression of SMC marker genes in various SMC model systems in vitro...
- Birsoy K, Chen Z, Friedman J. Transcriptional regulation of adipogenesis by KLF4. Cell Metab. 2008;7:339-47 pubmed publisher..KLF4 is specifically induced in response to cAMP, which by itself can partially activate adipogenesis. These data suggest that KLF4 functions as an immediate early regulator of adipogenesis to induce C/EBPbeta. ..
- Rivero S, Díaz Guerra M, Monsalve E, Laborda J, Garcia Ramirez J. DLK2 is a transcriptional target of KLF4 in the early stages of adipogenesis. J Mol Biol. 2012;417:36-50 pubmed publisher..These results indicate that KLF4 mediates the transcriptional regulation of Dlk2 in response to IBMX during the early stages of adipogenesis. ..
- Curry McCoy T, Guidot D, Joshi P. Chronic alcohol ingestion in rats decreases Krüppel-like factor 4 expression and intracellular zinc in the lung. Alcohol Clin Exp Res. 2013;37:361-71 pubmed publisher..Furthermore, the dynamic decrease in the relative influence of GM-CSF versus TGF?1 could mediate the zinc deficiency and consequent cellular dysfunction that characterize the "alcoholic lung" phenotype. ..
- Aktug H, Uysal A, Yavasoglu A, Oltulu F, Akarca S, Yılmaz Dilsiz O, et al. The detrimental effects of diabetes on pluripotency determined by KLF4, SOX2, C-MYC and OCT4 immunoreactivity in rat testes. Adv Clin Exp Med. 2013;22:327-35 pubmed..This study clearly demonstrated that Klf4, Sox2 and Oct4 immunopositive cells in adult male rat testes manifested sustainable pluripotency and that diabetes has dramatically detrimental effects on this trait. ..
- Pérez Monter C, Martínez Armenta M, Miquelajauregui A, Furlan Magaril M, Varela Echavarria A, Recillas Targa F, et al. The Krüppel-like factor 4 controls biosynthesis of thyrotropin-releasing hormone during hypothalamus development. Mol Cell Endocrinol. 2011;333:127-33 pubmed publisher..Thus, our data indicate that Klf4 plays a key role in the maturation of TRH expression in hypothalamic neurons. ..
- Wong C, Hou P, Tseng S, Chien C, Wu K, Chen H, et al. Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells. Stem Cells. 2010;28:1510-7 pubmed publisher..Therefore, our findings demonstrate that hTERT is one of the major targets of KLF4 in cancer and stem cells to maintain long-term proliferation potential. ..
- Fang Y, Davies P. Site-specific microRNA-92a regulation of Kruppel-like factors 4 and 2 in atherosusceptible endothelium. Arterioscler Thromb Vasc Biol. 2012;32:979-87 pubmed publisher..miR-92a coregulates KLF4 and KLF2 expression in arterial endothelium and contributes to phenotype heterogeneity associated with regional atherosusceptibility and protection in vivo...
- Nie C, Li Y, Zhang X, Wang Z, Jiang W, Zhang Y, et al. SUMOylation of KLF4 acts as a switch in transcriptional programs that control VSMC proliferation. Exp Cell Res. 2016;342:20-31 pubmed publisher..These results demonstrated that SUMOylated KLF4 plays an important role in cell proliferation by reversing the transactivation action of KLF4 on p21 induced with PDGF-BB. ..
- Zhang R, Han M, Zheng B, Li Y, Shu Y, Wen J. Krüppel-like factor 4 interacts with p300 to activate mitofusin 2 gene expression induced by all-trans retinoic acid in VSMCs. Acta Pharmacol Sin. 2010;31:1293-302 pubmed publisher..KLF4 acetylation by p300 increased its activity to transactivate the mfn-2 promoter. ATRA induces KLF4 acetylation by p300 and increases the ability of KLF4 to transactivate the mfn-2 promoter in VSMCs. ..
- Lallès J, Orozco Solis R, Bolaños Jiménez F, de Coppet P, Le Drean G, Segain J. Perinatal undernutrition alters intestinal alkaline phosphatase and its main transcription factors KLF4 and Cdx1 in adult offspring fed a high-fat diet. J Nutr Biochem. 2012;23:1490-7 pubmed publisher..In conclusion, the adult intestine adapts to an HF diet differentially depending on early nutrition, jejunal AP and transcription factors being blunted in IUGR individuals fed HF. ..
- Ghaleb A, McConnell B, Nandan M, Katz J, Kaestner K, Yang V. Haploinsufficiency of Krüppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis. Cancer Res. 2007;67:7147-54 pubmed..Results from this study show that KLF4 plays an important role in promoting the development of intestinal adenomas in the presence of Apc(Min) mutation. ..
- Li Y, McClintick J, Zhong L, Edenberg H, Yoder M, Chan R. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood. 2005;105:635-7 pubmed..These findings verify the negative role of SOCS-3 on LIF signaling and provide a novel role for Klf4 in ES cell function. ..
- King K, Iyemere V, Weissberg P, Shanahan C. Krüppel-like factor 4 (KLF4/GKLF) is a target of bone morphogenetic proteins and transforming growth factor beta 1 in the regulation of vascular smooth muscle cell phenotype. J Biol Chem. 2003;278:11661-9 pubmed..marker expression, TGF-beta 1 and BMP-2, -4, and -6 all induced binding of the Krüppel-like transcription factor, GKLF/KLF4, to the TGF-beta control element...
- Kalra I, Alam M, Choudhary P, Pace B. Krüppel-like Factor 4 activates HBG gene expression in primary erythroid cells. Br J Haematol. 2011;154:248-59 pubmed publisher..Our data supports a model of antagonistic interaction of KLF4/CREBBP trans-factors in HBG regulation. ..
- Wassmann K, Mueller C, Becher U, Werner C, Jung A, Zimmer S, et al. Interaction of Inhibitor of DNA binding 3 (Id3) with Gut-enriched Krüppel-like factor (GKLF) and p53 regulates proliferation of vascular smooth muscle cells. Mol Cell Biochem. 2010;333:33-9 pubmed publisher..and its interaction with other redox-sensitive genes, the transcription factor Gut-enriched Krüppel-like factor (GKLF, KLF4) and the tumor suppressor gene p53 in the regulation of VSMC proliferation...
- Higaki Y, Schullery D, Kawata Y, Shnyreva M, Abrass C, Bomsztyk K. Synergistic activation of the rat laminin gamma1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1. Nucleic Acids Res. 2002;30:2270-9 pubmed..Using the bcn-1 element as a bait in the yeast one-hybrid screen, we cloned the gut-enriched Kruppel-like factor (GKLF or KLF4) from a rat mesangial cell library...
- Lee H, Lee D, Park S, Cho K, Bae H, Park J. Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E-cadherin via control of Krüppel-like factor 4 (KLF4) during dentinogenesis. J Biol Chem. 2014;289:28225-36 pubmed publisher..Our results indicate the important role of NFIC in regulating KLF4 during dentinogenesis...
- Liu Y, Zheng B, Zhang X, Nie C, Li Y, Wen J. Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell. Biochem Biophys Res Commun. 2013;436:162-8 pubmed publisher..In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs. ..
- Yoshida T, Yamashita M, Hayashi M. Kruppel-like factor 4 contributes to high phosphate-induced phenotypic switching of vascular smooth muscle cells into osteogenic cells. J Biol Chem. 2012;287:25706-14 pubmed publisher..Klf4 was also induced markedly in the calcified aorta of adenine-induced uremic rats. Results provide novel evidence that Klf4 mediates high phosphate-induced conversion of SMCs into osteogenic cells. ..
- Liao X, Haldar S, Lu Y, Jeyaraj D, Paruchuri K, Nahori M, et al. Krüppel-like factor 4 regulates pressure-induced cardiac hypertrophy. J Mol Cell Cardiol. 2010;49:334-8 pubmed publisher..Collectively, these studies implicate KLF4 as a novel transcriptional regulator that is indispensible for the heart's response to stress in vivo. ..
- Cheng W, She Z, Qin J, Guo J, Gong F, Zhang P, et al. Interferon Regulatory Factor 4 Inhibits Neointima Formation by Engaging Krüppel-Like Factor 4 Signaling. Circulation. 2017;136:1412-1433 pubmed publisher..Our findings suggest that this previously undiscovered IRF4-KLF4 axis plays a key role in vasculoproliferative pathology and may be a promising therapeutic target for the treatment of arterial restenosis. ..
- Zeng Y, Zhuang S, Gloddek J, Tseng C, Boss G, Pilz R. Regulation of cGMP-dependent protein kinase expression by Rho and Kruppel-like transcription factor-4. J Biol Chem. 2006;281:16951-61 pubmed..Regulation of PKG I expression by RhoA may explain decreased PKG I levels in vascular smooth muscle cells found in some models of hypertension and vascular injury. ..
- Sun S, Zheng B, Han M, Fang X, Li H, Miao S, et al. miR-146a and Krüppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation. EMBO Rep. 2011;12:56-62 pubmed publisher..These findings suggest that miR-146a and KLF4 form a feedback loop to regulate each other's expression and VSMC proliferation. ..
- Bin L, Deng L, Yang H, Zhu L, Wang X, Edwards M, et al. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation. PLoS ONE. 2016;11:e0167392 pubmed publisher..Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network. ..
- Yu K, Zheng B, Han M, Wen J. ATRA activates and PDGF-BB represses the SM22? promoter through KLF4 binding to, or dissociating from, its cis-DNA elements. Cardiovasc Res. 2011;90:464-74 pubmed publisher..In VSMCs, ATRA activates and PDGF-BB represses SM22? expression through KLF4 binding to, or dissociating from, its different cis-elements in an acetylation-dependent manner. ..
- Saifudeen Z, Dipp S, Fan H, El Dahr S. Combinatorial control of the bradykinin B2 receptor promoter by p53, CREB, KLF-4, and CBP: implications for terminal nephron differentiation. Am J Physiol Renal Physiol. 2005;288:F899-909 pubmed..These results demonstrate that combinatorial interactions among the transcription factors, CREB, p53, and KLF-4, and the coactivator CBP, may be critical for the regulation of B2R gene expression during terminal nephron differentiation. ..
- Cullingford T, Butler M, Marshall A, Tham E, Sugden P, Clerk A. Differential regulation of Krüppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines. Biochim Biophys Acta. 2008;1783:1229-36 pubmed publisher..The dynamic regulation of expression of multiple Klf family members in cardiac myocytes suggests that, as a family, they are actively involved in regulating phenotypic responses (hypertrophy and apoptosis) to extracellular stimuli. ..