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Klf2  -  Kruppel-like factor 2 (lung)

Mus musculus

Synonyms: Krueppel-like factor 2, Lklf, Lung krueppel-like factor
 
 
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Disease relevance of Klf2

  • Mice lacking LKLF die in utero between day 11.5 and 13.5 of embryonic life and exhibit retarded growth, craniofacial abnormalities, abdominal bleeding and signs of anaemia [1].
  • Mice lacking LKLF due to inactivation of LKLF by gene targeting die in utero at midgestation around day 12.5 due to severe hemorrhage, making it difficult to study the role of this transcription factor in lung development and function [2].
 

High impact information on Klf2

  • LKLF: A transcriptional regulator of single-positive T cell quiescence and survival [3].
  • LKLF-deficient T cells produced by gene targeting had a spontaneously activated phenotype and died in the spleen and lymph nodes from Fas ligand-induced apoptosis [3].
  • Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes [4].
  • These results reveal a novel aspect of TRAF2 function: by regulating the expression of genes, such as LKLF, TRAF2 controls cell sensitivity to apoptosis [5].
  • A high degree of similarity is noted in the zinc finger regions of LKLF and EKLF [6].
 

Biological context of Klf2

 

Anatomical context of Klf2

  • To examine later stages of lung development, the embryonic lethality due to germ line LKLF null mutation was circumvented by constructing LKLF homozygous null mouse embryonic stem cells, using a two-step gene targeting procedure, and determining whether these cells give rise to lung tissue [2].
  • In this study, we identify that a second family member, KLF2/Lung Krüppel-like factor (LKLF), as a negative regulator of adipocyte differentiation [8].
  • However, some genes which may play important roles in maintaining the pluripotency of ES cells (Kruppel-like factor 2, 4, 5, 9, myeloblast oncogene like2, ZFP 57, and Esg-1) were down-regulated [9].
 

Associations of Klf2 with chemical compounds

  • LKLF was found to be reexpressed following culture of activated CD8 T cells in certain cytokines (IL-2, IL-7) but not others (IL-12) known to influence CTL development [10].
 

Other interactions of Klf2

 

Analytical, diagnostic and therapeutic context of Klf2

  • To understand the role this novel transcription factor plays in development as well as tissue differentiation and function, animals lacking LKLF were produced using gene targeting technology [1].
  • However, in vitro organ culture of lung buds removed from 11.5-day-old LKLF(-/-) embryos show normal tracheobronchial tree formation [2].
  • The binding of these proteins to the highly conserved region of the KLF2 promoter element was tested by electrophoretic mobility supershift assays and chromatin immunoprecipitation analysis [7].
  • LKLF meets the criteria of an anti-atherosclerotic gene, mainly since expression is restricted to areas subjected to laminar flow as shown by in situ hybridization with anatomically well-defined specimens [11].

References

  1. Loss of LKLF function results in embryonic lethality in mice. Wani, M.A., Means, R.T., Lingrel, J.B. Transgenic Res. (1998) [Pubmed]
  2. Lung Kruppel-like factor, a zinc finger transcription factor, is essential for normal lung development. Wani, M.A., Wert, S.E., Lingrel, J.B. J. Biol. Chem. (1999) [Pubmed]
  3. LKLF: A transcriptional regulator of single-positive T cell quiescence and survival. Kuo, C.T., Veselits, M.L., Leiden, J.M. Science (1997) [Pubmed]
  4. Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. Das, H., Kumar, A., Lin, Z., Patino, W.D., Hwang, P.M., Feinberg, M.W., Majumder, P.K., Jain, M.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. TRAF2 exerts its antiapoptotic effect by regulating the expression of Krüppel-like factor LKLF. Lin, Y., Ryan, J., Lewis, J., Wani, M.A., Lingrel, J.B., Liu, Z.G. Mol. Cell. Biol. (2003) [Pubmed]
  6. Isolation of a gene encoding a functional zinc finger protein homologous to erythroid Krüppel-like factor: identification of a new multigene family. Anderson, K.P., Kern, C.B., Crable, S.C., Lingrel, J.B. Mol. Cell. Biol. (1995) [Pubmed]
  7. Kruppel-like factor 2 transcriptional regulation involves heterogeneous nuclear ribonucleoproteins and acetyltransferases. Ahmad, N., Lingrel, J.B. Biochemistry (2005) [Pubmed]
  8. The Krüppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. Banerjee, S.S., Feinberg, M.W., Watanabe, M., Gray, S., Haspel, R.L., Denkinger, D.J., Kawahara, R., Hauner, H., Jain, M.K. J. Biol. Chem. (2003) [Pubmed]
  9. Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons. Ahn, J.I., Lee, K.H., Shin, D.M., Shim, J.W., Lee, J.S., Chang, S.Y., Lee, Y.S., Brownstein, M.J., Lee, S.H., Lee, Y.S. Dev. Biol. (2004) [Pubmed]
  10. Expression of the transcription factor lung Krüppel-like factor is regulated by cytokines and correlates with survival of memory T cells in vitro and in vivo. Schober, S.L., Kuo, C.T., Schluns, K.S., Lefrancois, L., Leiden, J.M., Jameson, S.C. J. Immunol. (1999) [Pubmed]
  11. Focusing on transcription factor families in atherogenesis: the function of LKLF and TR3. Arkenbout, E.K., Dekker, R.J., de Vries, C.J., Horrevoets, A.J., Pannekoek, H. Thromb. Haemost. (2003) [Pubmed]
 
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