title: Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'.
abstract: 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.
authors.affiliation: Department of Genome Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Yagishita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Minako
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Yamadera
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Bae
authors.forename: Sayumi
authors.initials: S
authors.lastname: Toriyama
authors.forename: Rie
authors.initials: R
authors.lastname: Ikeda
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Kazuko
authors.initials: K
authors.lastname: Fujitani
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Yoo
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Tsuchimochi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohta
authors.forename: Natsumi
authors.initials: N
authors.lastname: Araya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Satoko
authors.initials: S
authors.lastname: Aratani
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Higashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sato
authors.forename: Haruki
authors.initials: H
authors.lastname: Senoo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Amano
authors.forename: Jaeseob
authors.initials: J
authors.lastname: Kim
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism*; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex