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Cytoplasmic destruction of p53 by the endoplasmic reticulum‐resident ubiquitin ligase ‘Synoviolin’
Author(s) -
Yamasaki Satoshi,
Yagishita Naoko,
Sasaki Takeshi,
Nakazawa Minako,
Kato Yukihiro,
Yamadera Tadayuki,
Bae Eunkyung,
Toriyama Sayumi,
Ikeda Rie,
Zhang Lei,
Fujitani Kazuko,
Yoo Eunkyung,
Tsuchimochi Kaneyuki,
Ohta Tomohiko,
Araya Natsumi,
Fujita Hidetoshi,
Aratani Satoko,
Eguchi Katsumi,
Komiya Setsuro,
Maruyama Ikuro,
Higashi Nobuyo,
Sato Mitsuru,
Senoo Haruki,
Ochi Takahiro,
Yokoyama Shigeyuki,
Amano Tetsuya,
Kim Jaeseob,
Gay Steffen,
Fukamizu Akiyoshi,
Nishioka Kusuki,
Tanaka Keiji,
Nakajima Toshihiro
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601490
Subject(s) - biology , endoplasmic reticulum , ubiquitin ligase , cytoplasm , microbiology and biotechnology , dna ligase , ubiquitin , ubiquitin protein ligases , endoplasmic reticulum associated protein degradation , biochemistry , enzyme , unfolded protein response , gene
Synoviolin, also called HRD1, is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum ‐associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin ‐null cells. Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin.