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Gene Review

BHLHE40  -  basic helix-loop-helix family, member e40

Homo sapiens

Synonyms: BHLHB2, Class B basic helix-loop-helix protein 2, Class E basic helix-loop-helix protein 40, DEC1, Differentially expressed in chondrocytes protein 1, ...
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Disease relevance of BHLHB2

  • Subtractive experiments and blotting analyses demonstrated that DEC1 was highly expressed in colon carcinomas, but not in the adjacent normal tissues [1].
  • Previous studies have shown that DEC1, a basic helix-loop-helix transcription factor, is induced by hypoxia in glioma cells (Ivanova, A. V., Ivanov, S. V., Danilkovitch-Miagkova, A., and Lerman, M. I. (2001) J. Biol. Chem. 276, 15306-15315) [2].
  • Silencing of Hsp27 in prostate cancer cells by siRNAmusical sharp2 increased apoptotic rates 2.4-4 fold and caused 40-76% inhibition of cell growth in LNCaP and PC-3 cells [3].
  • Results: DEC1 was specifically located in 40 (48.8%) lung adenocarcinoma tissues [4].

High impact information on BHLHB2


Biological context of BHLHB2

  • Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene expressions are regulated by multiple extracellular stimuli [6].
  • Stable transfectants with a tetracycline-inducible construct demonstrated that DEC1 caused proliferation inhibition, antagonized serum deprivation-induced apoptosis and selectively inhibited the activation of procaspases [1].
  • Several cell cycle blockers markedly induced DEC1 expression [1].
  • In the 5'-flanking region of the DEC1 gene, several transcriptional factor binding sites, including a cAMP-responsive element (CRE), were found using the transcription factor database [7].
  • The DEC1 gene locates at Chromosome 3p25.3--26 by the FISH method [7].

Anatomical context of BHLHB2

  • DEC1/BHLHB2 is a novel cAMP-inducible basic helix-loop-helix (bHLH) transcriptional factor isolated from human chondrocyte cultures by the subtraction method [Shen et al. (1997) Biochem. Biophys. Res. Commun. 236, 294--298] [7].
  • The selective suppression on the activation of procaspases 3, 7 and 9 over procaspase 8 suggests that DEC1-mediated anti-apoptosis is achieved by blocking apoptotic pathways initiated via the mitochondria [1].
  • In the present study, we found that hypoxia or CoCl(2) enhanced the mRNA expression of DEC2, as well as DEC1, within 24 h in chondrogenic ATDC5, 293T, and HeLa cells [2].
  • At 15-72hpf, DEC1 shows a specific and dynamic expression in the developing eyes, somites, pineal gland (epiphysis), heart, brain, spinal cord, notochord, pronephric duct, common cardinal vein and blood cells [8].
  • Aim: To explore the mechanism of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in the lung adenocarcinoma A549 cell line and its relationship with hypoxia-inducible factor 1alpha(HIF-1alpha) [4].

Associations of BHLHB2 with chemical compounds

  • These activities were highly correlated with the abundance of tetracycline-induced DEC1 [1].
  • Phylogenetic analysis and comparison of the gene structure showed that the DEC1 protein is a member of a new subgroup of the proline bHLH protein family that diverged earlier than other proline bHLH proteins including HES, hairy and E(spl) [7].
  • Two genes, DEC1 (similar to acetoacetate decarboxylase-encoding genes) and RED1 (similar to genes encoding members of the medium-chain dehydrogenase/reductase superfamily), were recovered [9].

Other interactions of BHLHB2

  • Both the BHLHB2 and BHLHB3 genes are widely expressed in both embryonic and adult tissues [6].
  • Although the DEC2 HRE did not have a cAMP response element-like or CACAG sequence, it showed a higher affinity for HIF-1 than did the DEC1 HRE [2].

Analytical, diagnostic and therapeutic context of BHLHB2


  1. Abundant expression of Dec1/stra13/sharp2 in colon carcinoma: its antagonizing role in serum deprivation-induced apoptosis and selective inhibition of procaspase activation. Li, Y., Zhang, H., Xie, M., Hu, M., Ge, S., Yang, D., Wan, Y., Yan, B. Biochem. J. (2002) [Pubmed]
  2. Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes. Miyazaki, K., Kawamoto, T., Tanimoto, K., Nishiyama, M., Honda, H., Kato, Y. J. Biol. Chem. (2002) [Pubmed]
  3. Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro. Rocchi, P., Jugpal, P., So, A., Sinneman, S., Ettinger, S., Fazli, L., Nelson, C., Gleave, M. BJU Int. (2006) [Pubmed]
  4. Embryo-chondrocyte expressed gene 1, downregulating hypoxia-inducible factor 1alpha, is another marker of lung tumor hypoxia. Zhang, L., Li, Q.Q. Acta Pharmacol. Sin. (2007) [Pubmed]
  5. DEC1 negatively regulates the expression of DEC2 through binding to the E-box in the proximal promoter. Li, Y., Xie, M., Song, X., Gragen, S., Sachdeva, K., Wan, Y., Yan, B. J. Biol. Chem. (2003) [Pubmed]
  6. Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene expressions are regulated by multiple extracellular stimuli. Yamada, K., Miyamoto, K. Front. Biosci. (2005) [Pubmed]
  7. Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1 x Stra13 x SHARP-2/BHLHB2. Teramoto, M., Nakamasu, K., Noshiro, M., Matsuda, Y., Gotoh, O., Shen, M., Tsutsumi, S., Kawamoto, T., Iwamoto, Y., Kato, Y. J. Biochem. (2001) [Pubmed]
  8. Cloning and developmental expression of the DEC1 ortholog gene in zebrafish. Yao, J., Wang, L., Chen, L., Zhang, S., Zhao, Q., Jia, W., Xue, J. Gene Expr. Patterns (2006) [Pubmed]
  9. A decarboxylase encoded at the Cochliobolus heterostrophus translocation-associated Tox1B locus is required for polyketide (T-toxin) biosynthesis and high virulence on T-cytoplasm maize. Rose, M.S., Yun, S.H., Asvarak, T., Lu, S.W., Yoder, O.C., Turgeon, B.G. Mol. Plant Microbe Interact. (2002) [Pubmed]
  10. 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]
  11. Molecular characterization of the novel basic helix-loop-helix protein DEC1 expressed in differentiated human embryo chondrocytes. Shen, M., Kawamoto, T., Yan, W., Nakamasu, K., Tamagami, M., Koyano, Y., Noshiro, M., Kato, Y. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
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