title: SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability.
abstract: 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.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Hong
authors.forename: Xinrong
authors.initials: X
authors.lastname: Xing
authors.forename: Shujing
authors.initials: S
authors.lastname: Li
authors.forename: Hailian
authors.initials: H
authors.lastname: Bi
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.forename: Alan K
authors.initials: AK
authors.lastname: Chang
authors.forename: Huijian
authors.initials: H
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D016895:Culture Media, Serum-Free; D006801:Humans; D058207:Sumoylation; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; C403671:DELEC1 protein, human; D025521:Tumor Suppressor Proteins