学术探索
学术期刊
新闻热点
数据分析
智能评审

TAK1 MAPK kinase kinase mediates transforming growth factor-β signaling by targeting SnoN oncoprotein for degradation

被引：35
作者：
Kajino, Taisuke
Omori, Emily
Ishii, Shunsuke
Matsumoto, Kunihiro
Ninomiya-Tsuji, Jun [1 ]
机构：
[1] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA
[2] Nagoya Univ, Grad Sch Sci, Dept Biol Mol, Nagoya, Aichi 4648602, Japan
[3] RIKEN, Tsukuba Inst, Genet Mol Lab, Ibaraki 3050074, Japan
来源：
JOURNAL OF BIOLOGICAL CHEMISTRY | 2007年 / 282卷 / 13期
关键词：
D O I：
10.1074/jbc.M700875200
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：
Transforming growth factor-beta (TGF-beta) regulates a variety of physiologic processes through essential intracellular mediators Smads. The SnoN oncoprotein is an inhibitor of TGF-beta signaling. SnoN recruits transcriptional repressor complex to block Smad-dependent transcriptional activation of TGF-beta-responsive genes. Following TGF-beta stimulation, SnoN is rapidly degraded, thereby allowing the activation of TGF-beta target genes. Here, we report the role of TAK1 as a SnoN protein kinase. TAK1 interacted with and phosphorylated SnoN, and this phosphorylation regulated the stability of SnoN. Inactivation of TAK1. prevented TGF-beta-induced SnoN degradation and impaired induction of the TGF-beta-responsive genes. These data suggest that TAK1 modulates TGF-beta-dependent cellular responses by targeting SnoN for degradation.
引用
收藏
页码：9475 / 9481
页数：7
相关论文
共 28 条
[1]   TGF-β induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation [J].
Bonni, S ;
Wang, HR ;
Causing, CG ;
Kavsak, P ;
Stroschein, SL ;
Luo, KX ;
Wrana, JL .
NATURE CELL BIOLOGY, 2001, 3 (06) :587-595
[2]   A transcriptional partner for MAD proteins in TGF-beta signalling [J].
Chen, X ;
Rubock, MJ ;
Whitman, M .
NATURE, 1996, 383 (6602) :691-696
[3]   HOW MAP KINASES ARE REGULATED [J].
COBB, MH ;
GOLDSMITH, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (25) :14843-14846
[4]   Transforming growth factor-β1 (TGF-β)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-β-activated kinase 1 and mitogen-activated protein kinase kinase 3 [J].
Edlund, S ;
Bu, SH ;
Schuster, N ;
Aspenström, P ;
Heuchel, R ;
Heldin, NE ;
ten Dijke, P ;
Heldin, CH ;
Landström, M .
MOLECULAR BIOLOGY OF THE CELL, 2003, 14 (02) :529-544
[5]   Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].
Elbashir, SM ;
Harborth, J ;
Lendeckel, W ;
Yalcin, A ;
Weber, K ;
Tuschl, T .
NATURE, 2001, 411 (6836) :494-498
[6]   Involvement of the p38 mitogen-activated protein kinase pathway in transforming growth factor-β-induced gene expression [J].
Hanafusa, H ;
Ninomiya-Tsuji, J ;
Masuyama, N ;
Nishita, M ;
Fujisawa, J ;
Shibuya, H ;
Matsumoto, K ;
Nishida, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (38) :27161-27167
[7]   The TGFβ activated kinase TAK1 regulates vascular development in vivo [J].
Jadrich, JL ;
O'Connor, MB ;
Coucouvanis, E .
DEVELOPMENT, 2006, 133 (08) :1529-1541
[8]   TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop [J].
Kishimoto, K ;
Matsumoto, K ;
Ninomiya-Tsuji, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (10) :7359-7364
[9]   Ski/Sno and TGF-β signaling [J].
Liu, XD ;
Sun, Y ;
Weinberg, RA ;
Lodish, HF .
CYTOKINE & GROWTH FACTOR REVIEWS, 2001, 12 (01) :1-8
[10]   Ski and SnoN:: negative regulators of TGF-β signaling [J].
Luo, KX .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (01) :65-70
123