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アフリカツメガエルMyt1N末端ドメインの制御機構の研究

相羽, 行人 AIBA, Yukito アイバ, ユキト 九州大学

2022.03.23

概要

Immature animal oocytes are naturally arrested at the first meiotic prophase (Pro-I), which corr esponds to the G2 phase of the cell cycle. In Xenopus oocytes, Myt1 kinase phosphorylates and inac tivates cyclin-dependent kinase 1 (Cdk 1) at Pro-I, ther eby preventing oocytes from enter ing meiosis I (MI) pr ematur ely. Previous studies have shown that, upon resuming MI, Cdk1 and p90rsk, which is a downstream kinase of the Mos-MAPK pathway, in turn phosphorylate the C-term inal r egion of Myt1, to suppress its activity, thereby ensuring high Cdk1 activity during M phase. However, the roles of the N-term inal region of Myt1 dur ing meiosis and mitosis remain to be elucidated. In the present study, I show that the N-terminal region of Myt1 participates in the regulation of Myt1 activity in the Xenopus cell cycle. In particular, I found that a short, conserved sequence in the N-term inal region, term ed her e as the PAYF motif, is r equir ed for the normal ac tivity of Myt1 in oocytes. Furtherm ore, multiple phosphorylations by Cdk 1 at the Myt1 N-terminal r egion wer e found to be involved in the negative regulation of Myt1. In particular, phosphorylations at Thr 11 and Thr16 of Myt1, which ar e adjac ent to the PAYF motif, were found to be important for the inactivation of Myt1 in the M phase of the cell cycle. These results suggest that in addition to the regulation of Myt1 activity via the C-terminal region, the N-terminal region of Myt1 also plays an important role in the regulation of Myt1 activity.

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