Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor expression

Fuyuki Sato, Ujjal Kumar Bhawal, Takeshi Kawamoto, Katsumi Fujimoto, Tadaatsu Imaizumi, Tadanobu Imanaka, Jun Kondo, Satoru Koyanagi, Mitsuhide Noshiro, Hidemi Yoshida, Tomomi Kusumi, Yukio Kato, Hiroshi Kijima

研究成果: Contribution to journalArticle査読

65 被引用数 (Scopus)

抄録

DEC1 (BHLHB2/Sharp2/Stra13) and DEC2 (BHLHB3/Sharp1) are basic-helix-loop-helix (bHLH) transcription factors, involved in cellular differentiation, responses to hypoxia and circadian rhythms. We recently showed that the expression of DEC1 and DEC2 was up-regulated by hypoxia; however, the functions of these two factors under hypoxic conditions have not been elucidated in detail. It is well established that the expression of vascular endothelial growth factor (VEGF) is up-regulated by hypoxia, and the expression of VEGF in response to hypoxia depends on transcriptional activation by a heterodimer comprising hypoxia-inducible factor 1α (HIF-1α) and arylhydrocarbon receptor nuclear translocator 1 (ARNT1). In the present study, we showed that DEC2, but not DEC1, suppressed VEGF gene expression under hypoxic conditions. DEC2 protein was co-immunoprecipitated with HIF-1α but not with ARNT1. The binding of HIF-1α to the hypoxia response element (HRE) in the VEGF promoter was decreased by DEC2 over-expression, and increased by DEC2 knockdown. We also showed that the circadian expression of VEGF showed a reciprocal pattern to that of DEC2 in cartilage. DEC2 had a circadian oscillation in implanted Sarcoma 180 cells. We conclude that DEC2 negatively regulates VEGF expression and plays an important role in the pathological conditions in which VEGF is involved. Journal compilation

本文言語英語
ページ(範囲)131-144
ページ数14
ジャーナルGenes to Cells
13
2
DOI
出版ステータス出版済み - 2 2008

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 細胞生物学

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