TAK1 activation of alpha-TAT1 and microtubule hyperacetylation control AKT signaling and cell growth

• DOI: 10.1038/s41467-018-04121-y
• Publication Date: 2018-04-23T11:25:00Z
• Authors: Nirav Shah; Sanjay Kumar; Naveed Zaman; Christopher C. Pan; Jeffrey C. Bloodw...; Wei Lei; John M. Streicher; Nadine Hempel; Karthikeyan Mythreye; Nam Y. Lee
• Keywords: Acetyltransferases

Acetylation of microtubules (MT) confers mechanical stability necessary for numerous functions including cell cycle and intracellular transport. Although αTAT1 is a major MT acetyltransferase, how this enzyme regulated remains much less clear. Here we report TGF-β-activated kinase 1 (TAK1) as key activator αTAT1. TAK1 directly interacts with phosphorylates at Ser237 to critically enhance its catalytic activity, mutating site alanine abrogates, whereas phosphomimetic induces hyperacetylation across types. Using custom phospho-αTAT1-Ser237 antibody, screen various mouse tissues discover that brain contains some the highest TAK1-dependent which, accordingly, diminished rapidly upon intra-cerebral injection inhibitor. Lastly, show selectively inhibits AKT suppress mitogenic metabolism-related pathways through MT-based mechanisms in culture vivo. Collectively, our findings support fundamental new role TGF-β signaling MT-related disease.