Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation.
Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation.
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DOI：
10.1083/jcb.200705148
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发表时间：
2008-03-24
影响因子：
7.8
通讯作者：
Hirotsune, Shinji
中科院分区：
文献类型：
--
作者：
Toyo-oka, Kazuhito;Mori, Daisuke;Yano, Yoshihisa;Shiota, Masayuki;Iwao, Hiroshi;Goto, Hidemasa;Inagaki, Masaki;Hiraiwa, Noriko;Muramatsu, Masami;Wynshaw-Boris, Anthony;Yoshiki, Atsushi;Hirotsune, Shinji
蛋白磷酸酶4催化亚基（PP 4c）是一种与PP 2A相关的丝氨酸/苏氨酸蛋白磷酸酶，在多种细胞过程中具有重要功能，包括微管（MT）生长/组织、凋亡和肿瘤坏死因子信号传导。在这项研究中，我们报告说，NDEL 1是一个底物的PP 4c，和PP 4c选择性去磷酸化NDEL 1在Cdk 1网站。我们还表明，PP 4c负调控Cdk 1活性的中心体。PP 4c的靶向破坏揭示了MT的无序和无序的MT阵列。PP 4c的缺失导致Cdk 1在间期的非程序性激活，这导致NDEL 1的异常磷酸化。此外，异常的NDEL 1磷酸化促进了katanin p60向中心体的过度募集，这表明MT缺陷可能归因于katanin p60过量。Cdk 1、NDEL 1或katanin p60的抑制挽救了由PP 4抑制引起的缺陷性MT组织。我们的工作揭示了一个独特的调节机制MT组织PP 4c通过其目标Cdk 1和NDEL 1通过调节katanin p60的分布。
Protein phosphatase 4 catalytic subunit (PP4c) is a PP2A-related protein serine/threonine phosphatase with important functions in a variety of cellular processes, including microtubule (MT) growth/organization, apoptosis, and tumor necrosis factor signaling. In this study, we report that NDEL1 is a substrate of PP4c, and PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome. Targeted disruption of PP4c reveals disorganization of MTs and disorganized MT array. Loss of PP4c leads to an unscheduled activation of Cdk1 in interphase, which results in the abnormal phosphorylation of NDEL1. In addition, abnormal NDEL1 phosphorylation facilitates excessive recruitment of katanin p60 to the centrosome, suggesting that MT defects may be attributed to katanin p60 in excess. Inhibition of Cdk1, NDEL1, or katanin p60 rescues the defective MT organization caused by PP4 inhibition. Our work uncovers a unique regulatory mechanism of MT organization by PP4c through its targets Cdk1 and NDEL1 via regulation of katanin p60 distribution.
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影响因子：
21.3
作者：
Jackman, M;Lindon, C;Pines, J
通讯作者：
Pines, J
影响因子：
7.5
作者：
Bornens, M
通讯作者：
Bornens, M
影响因子：
9.2
作者：
Berrueta, L;Tirnauer, JS;Bierer, BE
通讯作者：
Bierer, BE
影响因子：
64.5
作者：
Hartman, JJ;Mahr, J;McNally, FJ
通讯作者：
McNally, FJ
影响因子：
64.8
作者：
Chapman, DL;Papaioannou, VE
通讯作者：
Papaioannou, VE