Center for Integrated Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.
J Biochem. 2012 Feb;151(2):157-66. doi: 10.1093/jb/mvr123. Epub 2011 Oct 5.
Transforming growth factor β-activated protein kinase 1 (TAK1)-binding protein 2 (TAB2) and its close homolog TAB3 are initially characterized as adapter proteins essential for TAK1 activation in response to interleukin-1β and tumour necrosis factor-α. However, the physiological roles of TAB2 and TAB3 are still not fully understood. Here we report that TAB2 and TAB3 bind to Beclin1 and colocalize in the cytoplasm. TAB2 also interacts with ATG13 and is phosphorylated by ULK1. Overexpression of TAB2 or TAB3 induces punctate localization of ATG5 under the normal culture condition. Knockdown of TAB2 and TAB3 results in the decrease in endogenous protein level of p62/SQSTM1 under the normal culture condition, while overexpression of TAB2 results in the accumulation of p62/SQSTM1 independently of TAK1. The decrease of p62/SQSTM1 induced by the knockdown of TAB2 and TAB3 is largely dependent on ATG5. These results suggest that TAB2 and TAB3 negatively regulate autophagy independently of TAK1 activity.
转化生长因子 β 激活蛋白激酶 1（TAK1）结合蛋白 2（TAB2）及其密切同源物 TAB3 最初被表征为衔接蛋白，对于白细胞介素 1β 和肿瘤坏死因子-α 刺激下 TAK1 的激活至关重要。然而，TAB2 和 TAB3 的生理作用仍未完全阐明。本文报道 TAB2 和 TAB3 与 Beclin1 结合并在细胞质中共定位。TAB2 还与 ATG13 相互作用，并被 ULK1 磷酸化。TAB2 或 TAB3 的过表达在正常培养条件下诱导 ATG5 点状定位。在正常培养条件下，TAB2 和 TAB3 的敲低导致内源性 p62/SQSTM1 蛋白水平下降，而 TAB2 的过表达导致 p62/SQSTM1 的积累，而不依赖于 TAK1。TAB2 和 TAB3 敲低诱导的 p62/SQSTM1 减少在很大程度上依赖于 ATG5。这些结果表明 TAB2 和 TAB3 独立于 TAK1 活性负调控自噬。
