Journal article
Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation
The Journal of cell biology, v 180(6), pp 1133-1147
24 Mar 2008
PMID: 18347064
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation
- Creators
- Kazuhito Toyo-oka - Osaka City UniversityDaisuke Mori - Osaka City UniversityYoshihisa Yano - Osaka City UniversityMasayuki Shiota - Osaka City UniversityHiroshi Iwao - Osaka City UniversityHidemasa Goto - Aichi Cancer CenterMasaki Inagaki - Aichi Cancer CenterNoriko Hiraiwa - RIKEN BioResource Research CenterMasami Muramatsu - Saitama Medical UniversityAnthony Wynshaw-Boris - University of California, San FranciscoAtsushi Yoshiki - RIKEN BioResource Research CenterShinji Hirotsune - Osaka City University
- Publication Details
- The Journal of cell biology, v 180(6), pp 1133-1147
- Publisher
- Rockefeller Univ Press
- Number of pages
- 15
- Grant note
- 19057010 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000254295400009
- Scopus ID
- 2-s2.0-41549164372
- Other Identifier
- 991020099252004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology