kruppel like transcription factors


Summary: A family of zinc finger transcription factors that share homology with Kruppel protein, Drosophila. They contain a highly conserved seven amino acid spacer sequence in between their ZINC FINGER MOTIFS.

Top Publications

  1. ALONZO E, Gottschalk R, Das J, Egawa T, Hobbs R, Pandolfi P, et al. Development of promyelocytic zinc finger and ThPOK-expressing innate gamma delta T cells is controlled by strength of TCR signaling and Id3. J Immunol. 2010;184:1268-79 pubmed publisher
    ..This study defines the factors that control the propensity of the immune system to produce potentially disease-causing T cell subsets. ..
  2. Chen Z, Lei T, Chen X, Zhang J, Yu A, Long Q, et al. Porcine KLF gene family: Structure, mapping, and phylogenetic analysis. Genomics. 2010;95:111-9 pubmed publisher
    ..The current work represents the first comprehensive study of KLF genes in pigs and provides a foundation for future studies concerning structural, functional, and evolutionary analyses of KLF gene family. ..
  3. Vermot J, Forouhar A, Liebling M, Wu D, Plummer D, Gharib M, et al. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLoS Biol. 2009;7:e1000246 pubmed publisher
  4. Miao L, Song Z, Jin L, Zhu Y, Wen L, Wu M. ARF antagonizes the ability of Miz-1 to inhibit p53-mediated transactivation. Oncogene. 2010;29:711-22 pubmed publisher
  5. Shen B, Smith R, Hsu Y, Chao L, Chao J. Kruppel-like factor 4 is a novel mediator of Kallistatin in inhibiting endothelial inflammation via increased endothelial nitric-oxide synthase expression. J Biol Chem. 2009;284:35471-8 pubmed publisher
    ..This study provides a new target for modulating endothelial function in vascular disease. ..
  6. Brey C, Nelder M, Hailemariam T, Gaugler R, Hashmi S. Krüppel-like family of transcription factors: an emerging new frontier in fat biology. Int J Biol Sci. 2009;5:622-36 pubmed
  7. Truty M, Lomberk G, Fernandez Zapico M, Urrutia R. Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel-like factor 14 underscores the importance of a negative feedback mechanism in TGFbeta signaling. J Biol Chem. 2009;284:6291-300 pubmed publisher
  8. Sangodkar J, Shi J, Difeo A, Schwartz R, Bromberg R, Choudhri A, et al. Functional role of the KLF6 tumour suppressor gene in gastric cancer. Eur J Cancer. 2009;45:666-76 pubmed publisher
  9. Denver R, Williamson K. Identification of a thyroid hormone response element in the mouse Kruppel-like factor 9 gene to explain its postnatal expression in the brain. Endocrinology. 2009;150:3935-43 pubmed publisher
    ..Our study identifies a functional DR-4 T(3)RE located in the mouse Klf9 gene to explain its regulation by T(3) during mammalian brain development. ..

More Information


  1. McConnell B, Bialkowska A, Nandan M, Ghaleb A, Gordon F, Yang V. Haploinsufficiency of Krüppel-like factor 5 rescues the tumor-initiating effect of the Apc(Min) mutation in the intestine. Cancer Res. 2009;69:4125-33 pubmed publisher
  2. Zhang J, Yang C, Brey C, Rodriguez M, Oksov Y, Gaugler R, et al. Mutation in Caenorhabditis elegans Krüppel-like factor, KLF-3 results in fat accumulation and alters fatty acid composition. Exp Cell Res. 2009;315:2568-80 pubmed publisher
    ..We present the first clear in vivo evidence supporting essential regulatory roles of KLF-3 in fat storage in C. elegans and shed light on the human equivalent in disease-gene association. ..
  3. Oh S, Huang X, Liu J, Litingtung Y, Chiang C. Shh and Gli3 activities are required for timely generation of motor neuron progenitors. Dev Biol. 2009;331:261-9 pubmed publisher
  4. Tallack M, Keys J, Humbert P, Perkins A. EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2. J Biol Chem. 2009;284:20966-74 pubmed publisher
    ..Finally, we propose direct regulation of the E2f2 enhancer is a generic mechanism by which many KLFs regulate proliferation and differentiation. ..
  5. Kreslavsky T, Savage A, Hobbs R, Gounari F, Bronson R, Pereira P, et al. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of gammadelta T cells with restricted TCR diversity. Proc Natl Acad Sci U S A. 2009;106:12453-8 pubmed publisher
    ..Interestingly, expression of this TCR transgene led to the development of spontaneous dermatitis. ..
  6. Verykokakis M, Boos M, Bendelac A, Adams E, Pereira P, Kee B. Inhibitor of DNA binding 3 limits development of murine slam-associated adaptor protein-dependent "innate" gammadelta T cells. PLoS ONE. 2010;5:e9303 pubmed publisher
    ..Our data provide novel insight into the requirements for development of Vgamma1.1+Vdelta6.3+ T cells and indicate a role for Id3 in repressing the response of "innate" gammadelta T cells to SAP-mediated expansion or survival. ..
  7. Nandan M, Yang V. The role of Krüppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells. Histol Histopathol. 2009;24:1343-55 pubmed publisher
    ..Further research is likely to provide additional insight into the mechanisms of somatic cell reprogramming and refinement of the technique with which to generate clinically relevant iPS cells. ..
  8. Wei Z, Yang Y, Zhang P, Andrianakos R, Hasegawa K, Lyu J, et al. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells. 2009;27:2969-78 pubmed publisher
    ..This study supports the idea that direct interactions between Klf4, Oct4, and Sox2 are critical for somatic cell reprogramming. ..
  9. Evans P, Chen X, Zhang W, Liu C. KLF4 interacts with beta-catenin/TCF4 and blocks p300/CBP recruitment by beta-catenin. Mol Cell Biol. 2010;30:372-81 pubmed publisher
    ..These results provide a deeper understanding of the regulation of beta-catenin in the intestine and will have important implications in cancer and stem cell research. ..
  10. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C, et al. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 2009;7:e54 pubmed publisher
    ..Thus, their development follows a unique pattern at the crossroad of NKT and gammadelta T cells. ..
  11. Suzuki T, Sawaki D, Aizawa K, Munemasa Y, Matsumura T, Ishida J, et al. Kruppel-like factor 5 shows proliferation-specific roles in vascular remodeling, direct stimulation of cell growth, and inhibition of apoptosis. J Biol Chem. 2009;284:9549-57 pubmed publisher
    ..These findings collectively suggest that KLF5 plays a central role in cardiovascular pathologies through direct and specific stimulation of cell growth as well as inhibition of apoptosis. ..
  12. Zheng B, Han M, Wen J. Role of Krüppel-like factor 4 in phenotypic switching and proliferation of vascular smooth muscle cells. IUBMB Life. 2010;62:132-9 pubmed publisher
    ..The focus of this review is to provide an overview for understanding the physiological and pathobiological roles of KLF4 in phenotypic switching and proliferation of VSMCs. ..
  13. He M, Han M, Zheng B, Shu Y, Wen J. Angiotensin II stimulates KLF5 phosphorylation and its interaction with c-Jun leading to suppression of p21 expression in vascular smooth muscle cells. J Biochem. 2009;146:683-91 pubmed publisher
    ..These results suggest that Ang II induces KLF5 phosphorylation mediated by the ERK signalling in VSMCs, which in turn stimulates the interaction of KLF5 with c-Jun, subsequently leads to the suppression of p21 expression. ..
  14. 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. ..
  15. Weinreich M, Takada K, Skon C, Reiner S, Jameson S, Hogquist K. KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine production and upregulation of bystander chemokine receptors. Immunity. 2009;31:122-30 pubmed publisher
    ..Our findings support a model where KLF2 regulates T cell trafficking by direct regulation of S1P(1) and CD62L and restrains spontaneous cytokine production in naive T cells. ..
  16. Nakamura Y, Migita T, Hosoda F, Okada N, Gotoh M, Arai Y, et al. Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression. Int J Cancer. 2009;125:1859-67 pubmed publisher
    ..038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures. ..
  17. Moore D, Blackmore M, Hu Y, Kaestner K, Bixby J, Lemmon V, et al. KLF family members regulate intrinsic axon regeneration ability. Science. 2009;326:298-301 pubmed publisher
    ..Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons. ..
  18. Lyssiotis C, Foreman R, Staerk J, Garcia M, Mathur D, Markoulaki S, et al. Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc Natl Acad Sci U S A. 2009;106:8912-7 pubmed publisher
    ..Ultimately, such compounds may provide mechanistic insight into the reprogramming process. ..
  19. Yamada T, Park C, Mamonkin M, Lacorazza H. Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2. Nat Immunol. 2009;10:618-26 pubmed publisher
    ..Our work describes the combinatorial effect of lymphocyte-intrinsic factors on the homeostasis, activation and homing of T cells. ..
  20. Young R, Swamynathan S, Boote C, Mann M, Quantock A, Piatigorsky J, et al. Stromal edema in klf4 conditional null mouse cornea is associated with altered collagen fibril organization and reduced proteoglycans. Invest Ophthalmol Vis Sci. 2009;50:4155-61 pubmed publisher
    ..The stroma also exhibits reduced interfibrillar proteoglycans throughout, which is possibly caused by increased expression of MMPs. ..
  21. Dong J, Chen C. Essential role of KLF5 transcription factor in cell proliferation and differentiation and its implications for human diseases. Cell Mol Life Sci. 2009;66:2691-706 pubmed publisher
    ..Due to its significant functions in cell proliferation, survival, and differentiation, KLF5 could be a potential diagnostic biomarker and therapeutic target for cancer and cardiovascular diseases. ..
  22. Meadows S, Salanga M, Krieg P. Kruppel-like factor 2 cooperates with the ETS family protein ERG to activate Flk1 expression during vascular development. Development. 2009;136:1115-25 pubmed publisher
  23. Du X, Rosenfield R, Qin K. KLF15 Is a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene. A potential link between regulation of testosterone production and fat stores in women. J Clin Endocrinol Metab. 2009;94:2594-601 pubmed publisher
    ..KLF15 is potentially a novel link between the regulation of testosterone production and fat stores by insulin in humans. ..
  24. Bhatia N, Thiyagarajan S, Elcheva I, Saleem M, Dlugosz A, Mukhtar H, et al. Gli2 is targeted for ubiquitination and degradation by beta-TrCP ubiquitin ligase. J Biol Chem. 2006;281:19320-6 pubmed
    ..These data identify beta-TrCP2 as a pivotal regulator of Gli2 expression and point to an important role for posttranslational modulation of GLI2 protein levels in Hh pathway-associated human prostate cancer. ..
  25. Swamynathan S, Katz J, Kaestner K, Ashery Padan R, Crawford M, Piatigorsky J. Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Mol Cell Biol. 2007;27:182-94 pubmed
  26. Du J, Yun C, Bialkowska A, Yang V. Protein inhibitor of activated STAT1 interacts with and up-regulates activities of the pro-proliferative transcription factor Krüppel-like factor 5. J Biol Chem. 2007;282:4782-93 pubmed
    ..Importantly, PIAS1 increased the ability of KLF5 to enhance cell proliferation in transfected cells. These results indicate that PIAS1 is a functional partner of KLF5 and enhances the ability of KLF5 to promote proliferation. ..
  27. Zhang H, Bialkowska A, Rusovici R, Chanchevalap S, Shim H, Katz J, et al. Lysophosphatidic acid facilitates proliferation of colon cancer cells via induction of Krüppel-like factor 5. J Biol Chem. 2007;282:15541-9 pubmed
    ..These results identify KLF5 as a target of LPA-mediated signaling and suggest a role of KLF5 in promoting proliferation of intestinal epithelia in response to LPA. ..
  28. Galan Caridad J, Harel S, Arenzana T, Hou Z, Doetsch F, Mirny L, et al. Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell. 2007;129:345-57 pubmed
    ..These studies identify Zfx as a shared transcriptional regulator of ESC and HSC, suggesting a common genetic basis of self-renewal in embryonic and adult SC. ..
  29. Natesampillai S, Fernandez Zapico M, Urrutia R, Veldhuis J. A novel functional interaction between the Sp1-like protein KLF13 and SREBP-Sp1 activation complex underlies regulation of low density lipoprotein receptor promoter function. J Biol Chem. 2006;281:3040-7 pubmed
  30. Roessler E, Ermilov A, Grange D, Wang A, Grachtchouk M, Dlugosz A, et al. A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2. Hum Mol Genet. 2005;14:2181-8 pubmed
  31. Otteson D, Liu Y, Lai H, Wang C, Gray S, Jain M, et al. Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci. 2004;45:2522-30 pubmed
  32. Krauss S, Foerster J, Schneider R, Schweiger S. Protein phosphatase 2A and rapamycin regulate the nuclear localization and activity of the transcription factor GLI3. Cancer Res. 2008;68:4658-65 pubmed publisher
  33. Swamynathan S, Davis J, Piatigorsky J. Identification of candidate Klf4 target genes reveals the molecular basis of the diverse regulatory roles of Klf4 in the mouse cornea. Invest Ophthalmol Vis Sci. 2008;49:3360-70 pubmed publisher
    ..These results establish Klf4 as an important node in the genetic network of transcription factors regulating the corneal homeostasis. ..
  34. Botella L, Sanz Rodriguez F, Komi Y, Fernandez L A, Varela E, Garrido Martin E, et al. TGF-beta regulates the expression of transcription factor KLF6 and its splice variants and promotes co-operative transactivation of common target genes through a Smad3-Sp1-KLF6 interaction. Biochem J. 2009;419:485-95 pubmed publisher
    ..These findings unveil a finely tuned network of interactions between KLF6, Sp1 and TGF-beta to regulate target genes. ..
  35. Gianakopoulos P, Skerjanc I. Cross talk between hedgehog and bone morphogenetic proteins occurs during cardiomyogenesis in P19 cells. In Vitro Cell Dev Biol Anim. 2009;45:566-72 pubmed publisher
    ..Thus, there is cross talk between the Hh and BMP signaling pathways and the Hh pathway appears important for timely cardiomyogenesis. ..
  36. Ky N, Lim C, Li J, Tam J, Hamza M, Zhao Y. KLF4 suppresses HDACi induced caspase activation and the SAPK pathway by targeting p57(Kip2). Apoptosis. 2009;14:1095-107 pubmed publisher
    ..Results of our study demonstrate an unexpected antiapoptotic function of KLF4, and suggest an important cell fate determinant following histone deacetylase inhibitor induced apoptosis. ..
  37. DU H, Sarno J, Taylor H. HOXA10 inhibits Kruppel-like factor 9 expression in the human endometrial epithelium. Biol Reprod. 2010;83:205-11 pubmed publisher
    ..HOXA10 directly and selectively repressed KLF9 expression in endometrial epithelial cells. HOXA10 repression of KLF9 likely contributes to the loss of sex steroid responsiveness in secretory-phase endometrial epithelium. ..
  38. Sobieszczuk D, Poliakov A, Xu Q, Wilkinson D. A feedback loop mediated by degradation of an inhibitor is required to initiate neuronal differentiation. Genes Dev. 2010;24:206-18 pubmed publisher
    ..These findings reveal a feedback loop mediated by degradation of an inhibitor that is essential for progenitors to undergo the transition to neuronal differentiation. ..
  39. Carette J, Pruszak J, Varadarajan M, Blomen V, Gokhale S, Camargo F, et al. Generation of iPSCs from cultured human malignant cells. Blood. 2010;115:4039-42 pubmed publisher
    ..This finding indicates that the therapeutic agent imatinib targets cells in a specific epigenetic differentiated cell state, and this may contribute to its inability to fully eradicate disease in chronic myeloid leukemia patients. ..
  40. Cheng Y, Liu X, Yang J, Lin Y, Xu D, Lu Q, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 2009;105:158-66 pubmed publisher
    ..These novel findings may have extensive implications for the diagnosis and therapy of a variety of proliferative vascular diseases. ..
  41. McDonald McGinn D, Feret H, Nah H, Bartlett S, Whitaker L, Zackai E. Metopic craniosynostosis due to mutations in GLI3: A novel association. Am J Med Genet A. 2010;152A:1654-60 pubmed publisher
  42. Kurita S, Mott J, Almada L, Bronk S, Werneburg N, Sun S, et al. GLI3-dependent repression of DR4 mediates hedgehog antagonism of TRAIL-induced apoptosis. Oncogene. 2010;29:4848-58 pubmed publisher
    ..In conclusion, these data provide evidence of a regulatory mechanism, which modulates TRAIL signaling in cancer cells and suggest new therapeutic approaches for TRAIL-resistant neoplasms. ..
  43. Hall J, Guo G, Wray J, Eyres I, Nichols J, Grotewold L, et al. Oct4 and LIF/Stat3 additively induce Krüppel factors to sustain embryonic stem cell self-renewal. Cell Stem Cell. 2009;5:597-609 pubmed publisher
    ..These findings indicate that Oct4 and Stat3 intersect in directing expression of Klf transcriptional regulators with overlapping properties that additively reinforce ground-state ESC pluripotency, identity, and self-renewal...
  44. Kim J, Jee M, Lee S, Han T, Kim B, Kang K, et al. Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control. PLoS ONE. 2009;4:e7166 pubmed publisher
    ..Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities. ..
  45. Vandeweyer G, Kooy R. Balanced translocations in mental retardation. Hum Genet. 2009;126:133-47 pubmed publisher
  46. Wilson A, Chueh A, Tögel L, Corner G, Ahmed N, Goel S, et al. Apoptotic sensitivity of colon cancer cells to histone deacetylase inhibitors is mediated by an Sp1/Sp3-activated transcriptional program involving immediate-early gene induction. Cancer Res. 2010;70:609-20 pubmed publisher
    ..Our findings link HDACi-induced apoptosis to activation of a Spl/Sp3-mediated response that involves derepression of a transcriptional network basally repressed in colon cancer...
  47. Dach K, Zovko J, Hogardt M, Koch I, van Erp K, Heesemann J, et al. Bacterial toxins induce sustained mRNA expression of the silencing transcription factor klf2 via inactivation of RhoA and Rhophilin 1. Infect Immun. 2009;77:5583-92 pubmed publisher
    ..Thus, bacteria exploit the RhoA-rhophilin signaling cascade to mediate sustained expression of the immunosuppressive transcription factor klf2. ..
  48. Ho L, Stojanovski A, Whetstone H, Wei Q, Mau E, Wunder J, et al. Gli2 and p53 cooperate to regulate IGFBP-3- mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors. Cancer Cell. 2009;16:126-36 pubmed publisher
    ..IGF signaling-meditated apoptosis regulates the progression to malignant chondrosarcoma. ..
  49. Harvey A, Armant D, Bavister B, Nichols S, Brenner C. Inner cell mass localization of NANOG precedes OCT3/4 in rhesus monkey blastocysts. Stem Cells Dev. 2009;18:1451-8 pubmed publisher
    ..This difference may also underlie observations that regulatory mechanisms in ESC differ between mice and primates...
  50. Herkert B, Dwertmann A, Herold S, Abed M, Naud J, Finkernagel F, et al. The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis. J Cell Biol. 2010;188:905-18 pubmed publisher
    ..Our data point to a tumor-suppressive pathway that weakens cell-cell and cell-matrix interactions in response to expression of Arf and that may thereby facilitate the elimination of cells harboring an oncogenic mutation. ..
  51. Jenal M, Trinh E, Britschgi C, Britschgi A, Roh V, Vorburger S, et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1. Mol Cancer Res. 2009;7:916-22 pubmed publisher
    ..Moreover, inhibition of E2F1 strongly reduced the expression of etoposide-induced HIC1. In conclusion, we identified HIC1 as novel E2F1 transcriptional target in DNA damage responses. ..
  52. Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods. 2009;6:377-82 pubmed publisher
    ..Finally, for Dicer1(-/-) and Ago2(-/-) (Eif2c2(-/-)) oocytes, we found that 1,696 and 1,553 genes, respectively, were abnormally upregulated compared to wild-type controls, with 619 genes in common...
  53. Gracia Sancho J, Villarreal G, Zhang Y, Yu J, Liu Y, Tullius S, et al. Flow cessation triggers endothelial dysfunction during organ cold storage conditions: strategies for pharmacologic intervention. Transplantation. 2010;90:142-9 pubmed publisher
    ..Supplementation of organ preservation solutions with pharmacologic agents that restore endothelial vasoprotective programs, by upregulating KLF2, may represent a significant advancement of current organ preservation techniques. ..