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

• Co-transfection with DEC1 repressed the activity of a DEC2 promoter reporter by as much as 90% [5].
• In stable transfectants, tetracycline-induced expression of DEC1 caused proportional decreases in the expression of DEC2 [5].
• Recently, we have reported that DEC1 is abundantly expressed in colon carcinomas but not in the adjacent normal tissues [5].
• Studies with deletion and site-directed mutants located, in the proximal promoter, an E-box motif that supported the DEC1-mediated repression [5].
• In addition to an HIF-1 binding site consensus sequence, the DEC1 HRE had cAMP response element-like and CACAG sequences, which were also involved in the transcription activation in response to HIF-1alpha [2].

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

• Enzymic assays and immunoblotting analyses demonstrated that induction of DEC1 by tetracycline significantly decreased the activation of procaspases 3, 7 and 9 but not procaspase 8 [1].
• Electrophoretic mobility shift assay and chromatin immunoprecipitation detected the presence of DEC1 in the survivin promoter [10].
• Northern blot analysis showed that DEC1 mRNA was expressed in various tissues including the cartilage, lung, spleen, and intestine, but not in the brain [11].
• Targeted disruption of DEC1 drastically reduced both T-toxin production and virulence of race T to T-cytoplasm maize, whereas specific inactivation of RED1 had no apparent effect on T-toxin production (as determined by bioassay) or on virulence [9].
• RT-PCR and immunocytochemistry were carried out to observe the DEC1 and HIF-1alpha mRNA and protein expression [4].

References