RRC ID 37632
著者 Miyazaki K, Inoue S, Yamada K, Watanabe M, Liu Q, Watanabe T, Adachi MT, Tanaka Y, Kitajima S.
タイトル Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells.
ジャーナル Nucleic Acids Res
Abstract Stress response gene ATF3 plays a pleiotropic role in determining cell fate in response to mitogenic or stress stimuli. An alternate promoter of the human ATF3 gene (designated P1 in this study) has recently been reported, which is located approximately 43.5 kb upstream of the previously reported P2 promoter. We showed here that the P1 promoter is highly conserved between human and mouse and is functional in response to various stimuli, whereas the P1 promoter was dominantly induced by serum and the P2 promoter was more efficiently activated in response to TGF-beta and oncogenic HRAS. The P1 promoter contains multiple transcriptional start sites, and the different 5'-UTRs markedly affected their translation in response to stress. In human prostate and Hodgkin Reed-Sternberg cancer cells with elevated expression of ATF3, the P1 promoter was constitutively activated and its chromatin structure was modified into active configuration. The differential usage of alternate promoters of the ATF3 gene at both transcriptional and translational level and the modification of chromatin structure may provide a novel mechanism for expressing ATF3 in determining cell fate during stress response and cancer.
巻・号 37(5)
ページ 1438-51
公開日 2009-4-1
DOI 10.1093/nar/gkn1082
PII gkn1082
PMID 19136462
PMC PMC2655689
MeSH 5' Untranslated Regions Activating Transcription Factor 3 / genetics* Activating Transcription Factor 3 / metabolism Animals Base Sequence Cell Line, Tumor Chromatin / metabolism Conserved Sequence DNA Damage Gene Expression Regulation* Gene Expression Regulation, Neoplastic* Humans Mice Molecular Sequence Data Oxidative Stress Promoter Regions, Genetic* Protein Biosynthesis Transcription Initiation Site Transcriptional Activation
IF 11.502
引用数 36
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MOLT-4(RCB0206) RAW 264(RCB0535)