scholarly journals Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation

2008 ◽  
Vol 180 (6) ◽  
pp. 1133-1147 ◽  
Author(s):  
Kazuhito Toyo-oka ◽  
Daisuke Mori ◽  
Yoshihisa Yano ◽  
Masayuki Shiota ◽  
Hiroshi Iwao ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Tumor Necrosis ◽  
Regulatory Mechanism ◽  
Catalytic Subunit ◽  
Related Protein ◽  
Microtubule Organization ◽  
Targeted Disruption ◽  
Cellular Processes ◽  
Tumor Necrosis Factor Signaling ◽  
Necrosis Factor

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.

scholarly journals The split protein phosphatase system

2018 ◽  
Vol 475 (23) ◽  
pp. 3707-3723 ◽  
Author(s):  
Anne Bertolotti
Keyword(s):  
Protein Phosphatase ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Post Translational Modification ◽  
Antagonistic Action ◽  
Cellular Processes ◽  
Depth Study ◽  
Split Protein ◽  
Phosphatase System ◽  
Physiological Substrates

Reversible phosphorylation of proteins is a post-translational modification that regulates all aspect of life through the antagonistic action of kinases and phosphatases. Protein kinases are well characterized, but protein phosphatases have been relatively neglected. Protein phosphatase 1 (PP1) catalyzes the dephosphorylation of a major fraction of phospho-serines and phospho-threonines in cells and thereby controls a broad range of cellular processes. In this review, I will discuss how phosphatases were discovered, how the view that they were unselective emerged and how recent findings have revealed their exquisite selectivity. Unlike kinases, PP1 phosphatases are obligatory heteromers composed of a catalytic subunit bound to one (or two) non-catalytic subunit(s). Based on an in-depth study of two holophosphatases, I propose the following: selective dephosphorylation depends on the assembly of two components, the catalytic subunit and the non-catalytic subunit, which serves as a high-affinity substrate receptor. Because functional complementation of the two modules is required to produce a selective holophosphatase, one can consider that they are split enzymes. The non-catalytic subunit was often referred to as a regulatory subunit, but it is, in fact, an essential component of the holoenzyme. In this model, a phosphatase and its array of mostly orphan substrate receptors constitute the split protein phosphatase system. The set of potentially generalizable principles outlined in this review may facilitate the study of these poorly understood enzymes and the identification of their physiological substrates.

117 THE COMPLEMENT c1q TUMOR NECROSIS FACTOR-RELATED PROTEIN 1 LEVEL IN PATIENTS WITH SLEEP APNEA AND PRIMARY ALDSTERONISM

2012 ◽  
Vol 30 ◽  
pp. e36
Author(s):  
Nanfang Li ◽  
Weiping Cheng ◽  
Xiaoguang Yao ◽  
Wanyong Ma ◽  
Zhitao Yan ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Related Protein ◽  
Complement C1q ◽  
Necrosis Factor

C1q/Tumor Necrosis Factor-Related Protein-9 Attenuates Diabetic Nephropathy and Kidney Fibrosis in db/db Mice

2020 ◽  
Vol 39 (6) ◽  
pp. 938-948 ◽  
Author(s):  
Hongyao Hu ◽  
Wei Li ◽  
Mingxin Liu ◽  
Jiarui Xiong ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Related Protein ◽  
Kidney Fibrosis ◽  
Necrosis Factor
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