The P-body component USP52/PAN2 is a novel regulator ofHIF1AmRNA stability

Bett, J. S., Ibrahim, A. F.M., Garg, A. K., Kelly, V., Pedrioli, P., Rocha, S. and Hay, R. T. (2013) The P-body component USP52/PAN2 is a novel regulator ofHIF1AmRNA stability. Biochemical Journal, 451(2), pp. 185-194. (doi: 10.1042/BJ20130026)

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Abstract

HIF1A (hypoxia-inducible factor 1α) is the master regulator of the cellular response to hypoxia and is implicated in cancer progression. Whereas the regulation of HIF1A protein in response to oxygen is well characterized, less is known about the fate of HIF1A mRNA. In the present study, we have identified the pseudo-DUB (deubiquitinating enzyme)/deadenylase USP52 (ubiquitin-specific protease 52)/PAN2 [poly(A) nuclease 2] as an important regulator of the HIF1A-mediated hypoxic response. Depletion of USP52 reduced HIF1A mRNA and protein levels and resulted in reduced expression of HIF1A-regulated hypoxic targets due to a 3′-UTR (untranslated region)-dependent poly(A)-tail-length-independent destabilization in HIF1A mRNA. MS analysis revealed an association of USP52 with several P-body (processing body) components and we confirmed further that USP52 protein and HIF1A mRNA co-localized with cytoplasmic P-bodies. Importantly, P-body dispersal by knockdown of GW182 or LSM1 resulted in a reduction of HIF1A mRNA levels. These data uncover a novel role for P-bodies in regulating HIF1A mRNA stability, and demonstrate that USP52 is a key component of P-bodies required to prevent HIF1A mRNA degradation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bett, Dr John
Authors: Bett, J. S., Ibrahim, A. F.M., Garg, A. K., Kelly, V., Pedrioli, P., Rocha, S., and Hay, R. T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Biochemical Journal
Publisher:Portland Press Ltd.
ISSN:0264-6021
ISSN (Online):1470-8728
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Biochemical Journal 451(2):185-194
Publisher Policy:Reproduced under a Creative Commons License

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