Mechanisms of growth arrest-induced TTBK2 activation and its role for ciliogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20910
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology; Functional biochemistry
• Research Institution: Tohoku University
• Principal Investigator: Nagai Tomoaki 東北大学, 生命科学研究科, 助教 (10723059)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 一次繊毛 / 中心体 / TTBK2 / Cep164 / 母中心小体

Outline of Final Research Achievements

Primary cilia are formed from the mother centriole in cellular quiescence. TTBK2 is a serine-threonine kinase that is essential for growth arrest-induced ciliogenesis, but its regulatory mechanism is largely unknown. In this study, I investigated the role of Cep164, a mother centriole protein known to recruit TTBK2 to the mother centriole, and ATR, a DNA damage response-related kinase, for TTBK2 activation. This study showed that an auto-interaction of TTBK2 between C-terminus and N-terminal kinase domain inhibits its kinase activity and that Cep164 interacts with the C-terminal region of TTBK2 and activate it through suppressing its autoinhibitory interaction. These results suggest that Cep164 plays an important role for not only the localization but also the activation of TTBK2.

Free Research Field

細胞生物学