Hirata Yusuke, Takahashi Miki, Morishita Tohru, Noguchi Takuya, Matsuzawa Atsushi
Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Int J Mol Sci. 2017 Jan 19;18(1):205. doi: 10.3390/ijms18010205.
Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is activated by growth factors and cytokines such as TGF-β, IL-1β, and TNF-α, and mediates a wide range of biological processes through activation of the nuclear factor-κB (NF-κB) and the mitogen-activated protein (MAP) kinase signaling pathways. It is well established that activation status of TAK1 is tightly regulated by forming a complex with its binding partners, TAK1-binding proteins (TAB1, TAB2, and TAB3). Interestingly, recent evidence indicates the importance of post-translational modifications (PTMs) of TAK1 and TABs in the regulation of TAK1 activation. To date, a number of PTMs of TAK1 and TABs have been revealed, and these PTMs appear to fine-tune and coordinate TAK1 activities depending on the cellular context. This review therefore focuses on recent advances in the understanding of the PTMs of the TAK1-TAB complex.
转化生长因子-β（TGF-β）激活激酶1（TAK1）是丝裂原活化蛋白激酶激酶激酶（MAPKKK）家族的成员，可被生长因子和细胞因子如TGF-β、IL-1β和TNF-α激活，并通过激活核因子-κB（NF-κB）和丝裂原活化蛋白（MAP）激酶信号通路介导广泛的生物学过程。众所周知，TAK1的激活状态通过与其结合伙伴TAK1结合蛋白（TAB1、TAB2和TAB3）形成复合物而受到严格调控。有趣的是，最近的证据表明TAK1和TABs的翻译后修饰（PTM）在TAK1激活调控中的重要性。迄今为止，已揭示了TAK1和TABs的多种PTM，这些PTM似乎根据细胞环境微调并协调TAK1的活性。因此，本综述重点关注TAK1-TAB复合物PTM研究的最新进展。
