Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E box sequence (5'-CANNTG-3') is found in the transcriptional regulatory region of a number of genes. Of the basic helix-loop-helix (bHLH) proteins binding to the E box sequence, class B of bHLH proteins, BHLHB2 (also referred to as the DEC1/Eip1/SHARP-2/Stra13/Clast5) and BHLHB3 (also referred to as the DEC2/SHARP-1/SHARP1), are transcription factors that contain a unique orange domain. These transcription factors repress the transcription of target genes not only via binding to the E box sequence but also via protein-protein interactions with other transcription factors. Both the BHLHB2 and BHLHB3 genes are widely expressed in both embryonic and adult tissues. Their gene expressions are regulated in a cell type-specific manner by various extracellular stimuli, such as growth factors, serum starvation, hypoxia, hormones, nutrient, cytokines, light, and infection. Therefore, these transcription factors play pivotal roles in multiple signaling pathways that impact many biological processes including development, cell differentiation, cell growth, cell death, oncogenesis, immune systems, circadian rhythm, and homeostasis. The structural features, functions, and biological roles of the novel bHLH transcription factors, BHLHB2 and BHLHB3, are discussed along with the mechanisms in which the genes encoding these factors are regulated.
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PMID:Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene expressions are regulated by multiple extracellular stimuli. 1597 May 69

Differentiated embryo-chondrocyte expressed gene 1 (DEC1, also known as sharp2, stra13, or BHLHB2) is a mammalian basic helix-loop-helix protein that is involved in many aspects of gene regulation through acting as a transcription factor. Changes in DEC1 expression levels have been implicated in the development of cancers. Using COS-7 cell, we showed that DEC1 can be modified by the small ubiquitin-like modifiers, SUMO1, 2 and 3. Two major SUMOylation sites (K(159) and K(279)) were identified in the C-terminal domain of DEC1. Substitution of either K(159) or K(279) with arginine reduced DEC1 SUMOylation, but substitution of both K(159) and K(279) abolished SUMOylation, and more protein appeared to be retained in the cytoplasm compared to wild-type DEC1. The expression of DEC1 was up-regulated after serum starvation as previously reported, but at the same time, serum starvation also led to more SUMOylation of DEC1. In MCF-7 cells SUMOylation also stabilized DEC1 through inhibiting its ubiquitination. Moreover, SUMOylation of DEC1 promoted its repression of CLOCK/BMAL1-mediated transcriptional activity through recruitment of histone deacetylase1. These findings suggested that posttranslational modification of DEC1 in the form of SUMOylation may serve as a key factor that regulates the function of DEC1 in vivo.
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PMID:SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability. 2182 89