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Bhlhe40  -  basic helix-loop-helix family, member e40

Mus musculus

Synonyms: Bhlhb2, C130042M06Rik, CR8, Class B basic helix-loop-helix protein 2, Class E basic helix-loop-helix protein 40, ...
 
 
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Disease relevance of Bhlhb2

  • Stra13 is expressed in embryonic as well as adult tissues derived from neuroectoderm, mesoderm, and endoderm and has been associated with response to hypoxia, suggesting a complex role for this protein and the highly related Sharp1/Dec2 protein in homeostatic regulation [1].
  • We report the cDNA cloning of Stra13, a novel retinoic acid (RA)-inducible gene from P19 embryonal carcinoma cells that encodes a basic helix-loop-helix (bHLH) protein that shows the highest sequence similarities to the Drosophila Hairy and Enhancer of split and mouse Hes proteins [2].
  • In vivo, Stra13 deficiency results in ineffective elimination of activated T and B cells, which accumulate progressively, leading to lymphoid organ hyperplasia [3].
  • Consequently, aging Stra13-/- mice develop autoimmune disease characterized by accumulation of spontaneously activated T and B cells, circulating autoantibodies, infiltration of T and B lymphocytes in several organs and immune complex deposition in glomeruli [3].
  • We have previously shown that Clast5 is rapidly down-regulated upon B cell activation and its overexpression inhibits cell cycle progression in B lymphoma cells [4].
 

High impact information on Bhlhb2

  • Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells [2].
  • During mouse embryogenesis, Stra13 RNA is expressed in the neuroectoderm, and also in a number of mesodermal and endodermal derivatives [2].
  • Our results raise the possibility that Stra13 could be involved as a repressor in a number of decision events occurring during differentiation of various cell lineages [2].
  • Defective T cell activation and autoimmune disorder in Stra13-deficient mice [3].
  • Our studies identify Stra13 as a key regulator of lymphocyte activation that is vital for maintenance of self-tolerance and for constraint of autoimmunity [3].
 

Biological context of Bhlhb2

  • A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation [5].
  • Stra13 homodimers repress transcription through class B E-box elements [1].
  • In this study, we have characterized the DNA-binding and transcriptional properties of the bHLH factor mSharp-1/DEC2. mSharp-1 belongs to the Hairy/Enhancer of Split subfamily of bHLH factors and exhibits the highest structural and sequence identity with Stra13 [6].
  • Indeed, Stra13 null mice develop age-induced autoimmunity as a result of impaired T-lymphocyte activation, leading ultimately to the accumulation of autoreactive T-cells and B-cells [1].
  • In addition, transient transfection experiments reveal that Stra13 represses transcription when bound to these and related sites [1].
 

Anatomical context of Bhlhb2

 

Associations of Bhlhb2 with chemical compounds

  • Indeed, the basic domain of Stra13 contains a proline residue at an unprecedented position [1].
  • DEC2 had high (97%) and moderate (52%) similarities in the bHLH region and the Orange domain with DEC1, respectively [11].
  • Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes [9].
  • Compared with control cells, cells overexpressing Stra13 showed markedly reduced NADPH-dependent superoxid anion generation [9].
  • Tetracycline-induced expression of DEC1 in stable lines proportionally increased the expression of survivin [12].
 

Regulatory relationships of Bhlhb2

 

Other interactions of Bhlhb2

  • The autofeedback loop of Dec1 may be interlocked with the core feedback loop of Per in some situations [5].
  • These data point to up-regulation of Dec1 and Dec2 by Clock in vivo [14].
  • Whereas Stra13 is known to regulate many important cellular functions and is known to cross-regulate biological responses to other basic helix-loop-helix containing transcription factors, including c-Myc and USF, it is unclear if this protein binds directly to DNA [1].
  • mSharp-1/DEC2, a basic helix-loop-helix protein functions as a transcriptional repressor of E box activity and Stra13 expression [6].
  • Moreover, mSharp-1 directly interacts with the transcriptional activator Sp1 and impairs Sp1 induction of Stra13 promoter [6].
 

Analytical, diagnostic and therapeutic context of Bhlhb2

References

  1. Stra13 homodimers repress transcription through class B E-box elements. St-Pierre, B., Flock, G., Zacksenhaus, E., Egan, S.E. J. Biol. Chem. (2002) [Pubmed]
  2. Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells. Boudjelal, M., Taneja, R., Matsubara, S., Bouillet, P., Dolle, P., Chambon, P. Genes Dev. (1997) [Pubmed]
  3. Defective T cell activation and autoimmune disorder in Stra13-deficient mice. Sun, H., Lu, B., Li, R.Q., Flavell, R.A., Taneja, R. Nat. Immunol. (2001) [Pubmed]
  4. Impaired lymphocyte development and function in Clast5/Stra13/DEC1-transgenic mice. Seimiya, M., Wada, A., Kawamura, K., Sakamoto, A., Ohkubo, Y., Okada, S., Hatano, M., Tokuhisa, T., Watanabe, T., Saisho, H., Tagawa, M., O-Wang, J. Eur. J. Immunol. (2004) [Pubmed]
  5. A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation. Kawamoto, T., Noshiro, M., Sato, F., Maemura, K., Takeda, N., Nagai, R., Iwata, T., Fujimoto, K., Furukawa, M., Miyazaki, K., Honma, S., Honma, K., Kato, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  6. mSharp-1/DEC2, a basic helix-loop-helix protein functions as a transcriptional repressor of E box activity and Stra13 expression. Azmi, S., Sun, H., Ozog, A., Taneja, R. J. Biol. Chem. (2003) [Pubmed]
  7. Clast5/Stra13 is a negative regulator of B lymphocyte activation. Seimiya, M., Bahar, R., Wang, Y., Kawamura, K., Tada, Y., Okada, S., Hatano, M., Tokuhisa, T., Saisho, H., Watanabe, T., Tagawa, M., O-Wang, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  8. 57Arg in the bHLH transcription factor DEC2 is essential for the suppression of CLOCK/BMAL2-mediated transactivation. Kondo, J., Sato, F., Fujimoto, K., Kusumi, T., Imanaka, T., Kawamoto, T., Uk, B., Noshiro, M., Kato, Y., Sato, T., Kijima, H. Int. J. Mol. Med. (2006) [Pubmed]
  9. Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes. Bek, M.J., Wahle, S., Müller, B., Benzing, T., Huber, T.B., Kretzler, M., Cohen, C., Busse-Grawitz, A., Pavenstädt, H. FASEB J. (2003) [Pubmed]
  10. Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages. Shen, M., Yoshida, E., Yan, W., Kawamoto, T., Suardita, K., Koyano, Y., Fujimoto, K., Noshiro, M., Kato, Y. J. Biol. Chem. (2002) [Pubmed]
  11. Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins. Fujimoto, K., Shen, M., Noshiro, M., Matsubara, K., Shingu, S., Honda, K., Yoshida, E., Suardita, K., Matsuda, Y., Kato, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter. Li, Y., Xie, M., Yang, J., Yang, D., Deng, R., Wan, Y., Yan, B. Oncogene (2006) [Pubmed]
  13. Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Yun, Z., Maecker, H.L., Johnson, R.S., Giaccia, A.J. Dev. Cell (2002) [Pubmed]
  14. Dec1 and Dec2 expression is disrupted in the suprachiasmatic nuclei of Clock mutant mice. Butler, M.P., Honma, S., Fukumoto, T., Kawamoto, T., Fujimoto, K., Noshiro, M., Kato, Y., Honma, K. J. Biol. Rhythms (2004) [Pubmed]
  15. Cytokine response gene 8 (CR8) regulates the cell cycle G1-S phase transition and promotes cellular survival. Beadling, C., Cereseto, A., Fan, W., Naramura, M., Smith, K.A. Oncogene (2001) [Pubmed]
  16. Constitutively active signal transducer and activator of transcription 5 can replace the requirement for growth hormone in adipogenesis of 3T3-F442A preadipocytes. Shang, C.A., Waters, M.J. Mol. Endocrinol. (2003) [Pubmed]
  17. The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumour grade in human breast cancers. Chakrabarti, J., Turley, H., Campo, L., Han, C., Harris, A.L., Gatter, K.C., Fox, S.B. Br. J. Cancer (2004) [Pubmed]
 
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