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Basic helix‐loop‐helix transcription factor DEC1 negatively regulates cyclin D1
Author(s) -
Bhawal Ujjal K,
Sato Fuyuki,
Arakawa Yuki,
Fujimoto Katsumi,
Kawamoto Takeshi,
Tanimoto Keiji,
Ito Yumi,
Sasahira Tomonori,
Sakurai Takashi,
Kobayashi Masaru,
Kashima Isamu,
Kijima Hiroshi,
Kuniyasu Hiroki,
Abiko Yoshimitsu,
Kato Yukio,
Sato Sadao
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2878
Subject(s) - cyclin d1 , transcription factor , biology , basic helix loop helix , microbiology and biotechnology , cyclin a , protein kinase b , cyclin a2 , cancer research , cell cycle , phosphorylation , gene , genetics , dna binding protein
DEC1 (also known as Stra13/Bhlhb2/Sharp2) and DEC2 (also known as Bhlhb3/Sharp1) are two paralogous basic helix‐loop‐helix (bHLH) transcriptional regulators which exhibit a robust circadian gene expression pattern in the suprachiasmatic nucleus (SCN) and in peripheral organs. DEC1 has been suggested to play key roles in mammalian cell differentiation, the cell cycle and circadian regulation, hypoxia response, and carcinogenesis. Here we show that DEC1 overexpression exhibits delayed wound healing and reduces cell proliferation, migration, and invasion. DEC1 strongly repressed the promoter activity of cyclin D1. We further identify a possible DEC‐response element in the cyclin D1 promoter region, and confirmed the direct binding of DEC1 to that element. Forced expression of DEC1 efficiently repressed the cyclin D1 promoter and expression. Our clinical data provide the first evidence that there is a strong inverse correlation between DEC1 and cyclin D1 expression in oral cancer, and DEC1 expression significantly correlated with clinicopathological parameters. We suggest that radiation‐induced DEC1 overexpression and Akt phosphorylation in cancer cells are mediated via PI‐3K signalling. Overexpression of DEC1 activates the PI‐3K/Akt signalling pathway through reactive oxygen species (ROS). Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.