COMMD1 promotes the ubiquitination of NF-κB subunits through a cullin-containing ubiquitin ligase

被引:222
作者
Maine, Gabriel N.
Mao, Xicheng
Komarck, Christine M.
Burstein, Ezra
机构
[1] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Mol Mech Dis Program, Ann Arbor, MI 48109 USA
[3] Ann Arbor VA Med Ctr, Gastroenterol Sect, Ann Arbor, MI USA
关键词
COMMD1; cullin; NF-kappa B; transcription; ubiquitination;
D O I
10.1038/sj.emboj.7601489
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
NF-kappa B is a pleiotropic transcription factor involved in multiple processes, including inflammation and oncogenesis. We have previously reported that COMMD1 represses kappa B-dependent transcription by negatively regulating NF-kappa B-chromatin interactions. Recently, ubiquitination of NF-kappa B subunits has been similarly implicated in the control of NF-kappa B recruitment to chromatin. We report here that COMMD1 accelerates the ubiquitination and degradation of NF-kappa B subunits through its interaction with a multimeric ubiquitin ligase containing Elongins B and C, Cul2 and SOCS1 (ECSSOCS1). COMMD1-deficient cells demonstrate stabilization of RelA, greater nuclear accumulation of RelA after TNF stimulation, de-repression of several kappa B-responsive genes, and enhanced NF-kappa B-mediated cellular responses. COMMD1 binds to Cul2 in a stimulus-dependent manner and serves to facilitate substrate binding to the ligase by stabilizing the interaction between SOCS1 and RelA. Our data uncover that ubiquitination and degradation of NF-kappa B subunits by this COMMD1-containing ubiquitin ligase is a novel and critical mechanism of regulation of NF-kappa B-mediated transcription.
引用
收藏
页码:436 / 447
页数:12
相关论文
共 27 条
[11]   NF-κB at the crossroads of life and death [J].
Karin, M ;
Lin, A .
NATURE IMMUNOLOGY, 2002, 3 (03) :221-227
[12]   Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors [J].
Lois, C ;
Hong, EJ ;
Pease, S ;
Brown, EJ ;
Baltimore, D .
SCIENCE, 2002, 295 (5556) :868-872
[13]   Structure and function of a new STAT-induced STAT inhibitor [J].
Naka, T ;
Narazaki, M ;
Hirata, M ;
Matsumoto, T ;
Minamoto, S ;
Aono, A ;
Nishimoto, N ;
Kajita, T ;
Taga, T ;
Yoshizaki, K ;
Akira, S ;
Kishimoto, T .
NATURE, 1997, 387 (6636) :924-929
[14]   The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins [J].
Pause, A ;
Lee, S ;
Worrell, RA ;
Chen, DYT ;
Burgess, WH ;
Linehan, WM ;
Klausner, RD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) :2156-2161
[15]   SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2 [J].
Rui, LY ;
Yuan, MS ;
Frantz, D ;
Shoelson, S ;
White, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (44) :42394-42398
[16]   Regulation of NF-κB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA [J].
Ryo, A ;
Suizu, F ;
Yoshida, Y ;
Perrem, K ;
Liou, YC ;
Wulf, G ;
Rottapel, R ;
Yamaoka, S ;
Lu, KP .
MOLECULAR CELL, 2003, 12 (06) :1413-1426
[17]   Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor κB response [J].
Saccani, S ;
Marazzi, I ;
Beg, AA ;
Natoli, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (01) :107-113
[18]   IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain [J].
Sakurai, H ;
Chiba, H ;
Miyoshi, H ;
Sugita, T ;
Toriumi, W .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (43) :30353-30356
[19]   Distinct roles of IκB proteins in regulating constitutive NF-κB activity [J].
Tergaonkar, V ;
Correa, RG ;
Ikawa, M ;
Verma, IM .
NATURE CELL BIOLOGY, 2005, 7 (09) :921-U89
[20]   Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1 [J].
Ungureanu, D ;
Saharinen, P ;
Junttila, I ;
Hilton, DJ ;
Silvennoinen, O .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (10) :3316-3326