TAK1 lysine 158 is required for TGF-β-induced TRAF6-mediated Smad-independent IKK/NF-κB and JNK/AP-1 activation.
TAK1 lysine 158 is required for TGF-β-induced TRAF6-mediated Smad-independent IKK/NF-κB and JNK/AP-1 activation.
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DOI：
10.1016/j.cellsig.2010.09.006
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发表时间：
2011-01
影响因子：
4.8
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Mao R;Fan Y;Mou Y;Zhang H;Fu S;Yang J
Lys63-linked TAK1多泛素化在TAK1激活的调控中起重要作用。traf6介导的Lys63-linked TAK1多泛素化已被证明是TGF-β诱导的TAK1激活所必需的。然而，在TGF-β-信号通路中，TAK1上的哪个赖氨酸残基是traf6介导的TAK1多泛素化受体位点尚不清楚。在这里，我们报道了TAK1上的赖氨酸158是TGF-β诱导的traf6介导的TAK1多泛素化和TAK1介导的IKK、JNK和p38激活所必需的。值得注意的是，与TAK1野生型和K34R突变体相比，TAK1 K158R突变体与TAB1共过表达未能诱导lys63相关的TAK1多泛素化。traf6诱导的K63-linked TAK1多泛素化被TAK1 K158R突变阻断，而不被K34R突变阻断。此外，在HeLa细胞中，TAK1 K158R突变抑制TGF-β诱导的TAK1多泛素化，而K34R突变不抑制。对TAK1野生型、K158R突变体或K34R突变体的TAK1缺陷小鼠胚胎成纤维细胞的重构表明，TAK1赖氨酸158残基是TGF-β诱导的IKK、p38和JNK激活所必需的。
Lys63-linked TAK1 polyubiquitination plays an essential role in the regulation of TAK1 activation. TRAF6-mediated Lys63-linked polyubiquitilation of TAK1 has been shown to be required for TGF-β-induced TAK1 activation. However, it remains unclear which lysine residue on TAK1 is TRAF6-mediated TAK1 polyubiquitination acceptor site in TGF-β-signaling pathway. Here we report that lysine 158 on TAK1 is required for TGF-β-induced TRAF6-mediated TAK1 polyubiquitination and TAK1-mediated IKK, JNK and p38 activation. Notably, in contrast to TAK1 wild-type and K34R mutant, TAK1 K158R mutant co-overexpression with TAB1 failed to induce Lys63-linked TAK1 polyubiquitination. TRAF6-induced K63-linked TAK1 polyubiquitination was blocked by TAK1 K158R mutation, but not by K34R mutation. Furthermore, TGF-β-induced TAK1 polyubiqutination was inhibited by TAK1 K158R mutation, but not by K34R mutation in HeLa cells. Reconstitution of TAK1-deficient mouse embryo fibroblast cells with TAK1 wild-type, K158R mutant, or K34R mutant reveals that TAK1 lysine 158 residue is required for TGF-β-induced IKK, p38 and JNK activation.
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影响因子：
56.9
作者：
Delhase, M;Hayakawa, M;Karin, M
通讯作者：
Karin, M
影响因子：
21.3
作者：
Sorrentino, Alessandro;Thakur, Noopur;Landstroem, Marene
通讯作者：
Landstroem, Marene
影响因子：
4.6
作者：
Jadrich, JL;O'Connor, MB;Coucouvanis, E
通讯作者：
Coucouvanis, E
影响因子：
15.9
作者：
Bornstein, Sophia;White, Ruth;Wang, Xiao-Jing
通讯作者：
Wang, Xiao-Jing
影响因子：
10.5
作者：
Shim, JH;Xiao, CC;Ghosh, S
通讯作者：
Ghosh, S