WWP2-WWP1 Ubiquitin Ligase Complex Coordinated by PPM1G Maintains the Balance between Cellular p73 and �Np73 Levels

Chaudhary, Neelam (2014) WWP2-WWP1 Ubiquitin Ligase Complex Coordinated by PPM1G Maintains the Balance between Cellular p73 and �Np73 Levels. Molecular and Cellular Biology, 34 (19). pp. 3754-3764. ISSN 0270-7306

[img] PDF
Molecular and Cellular Biology-2014-Chaudhary-3754.full.pdf - Published Version
Restricted to Registered users only

Download (1MB) | Request a copy

Abstract

The balance between transcription factor p73 and its functionally opposing N-terminally truncated �Np73 isoform is critical for cell survival, but the precise mechanism that regulates their levels is not clear. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase,WWP1, which specifically ubiquitinates and degrades �Np73. Further, we identified phosphatase PPM1G as a functional switch that controls the balance between monomeric WWP2 and a WWP2/WWP1 heterodimeric state in the cell. During cellular stress,WWP2 is inactivated, leading to upregulation of p73, whereas WWP2-WWP1 complex is intact to degrade �Np73, thus playing an important role in shifting the balance between p73 and �Np73. Collectively, our results reveal a new functional E3 ligase complex controlled by PPM1G that differentially regulates cellular p73 and �Np73

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 06 Aug 2019 03:53
Last Modified: 06 Aug 2019 03:53
URI: http://eprints.manipal.edu/id/eprint/154247

Actions (login required)

View Item View Item