Article
- The EMBO Journal (2006) 25, 1934 - 1944
- doi:10.1038/sj.emboj.7601079
Published online: 6 April 2006
Subject Category:
Poly(A) binding protein (PABP) homeostasis is mediated by the stability of its inhibitor, Paip2
Madoka Yoshida1,2, Kaori Yoshida1,2, Guennadi Kozlov1, Nadia S Lim1, Gregory De Crescenzo3, Zhiyu Pang4, Juan Jose Berlanga1,2, Avak Kahvejian1,2, Kalle Gehring1, Simon S Wing4 and Nahum Sonenberg1,2
- Department of Biochemistry, McGill University, Montreal, Quebec, Canada
- McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
- Département de génie chimique, École Polytechnique de Montréal, Montreal, Quebec, Canada
- Department of Medicine, McGill University, Montreal, Quebec, Canada
Correspondence to:
Nahum Sonenberg, Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Sir William Osler Street, Montreal, Quebec, Canada H3G 1Y6. Tel.: +1 514 398 7274; Fax: +1 514 398 1287; E-mail: nahum.sonenberg@mcgill.ca
Received 17 November 2005; Accepted 13 March 2006
Abstract
The poly(A)-binding protein (PABP) is a unique translation initiation factor in that it binds to the mRNA 3' poly(A) tail and stimulates recruitment of the ribosome to the mRNA at the 5' end. PABP activity is tightly controlled by the PABP-interacting protein 2 (Paip2), which inhibits translation by displacing PABP from the mRNA. Here, we describe a close interplay between PABP and Paip2 protein levels in the cell. We demonstrate a mechanism for this co-regulation that involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which leads to Paip2 ubiquitination. Supporting a critical role for EDD in Paip2 degradation, knockdown of EDD expression by siRNA leads to an increase in Paip2 protein stability. Thus, we demonstrate that the turnover of Paip2 in the cell is mediated by EDD and is regulated by PABP. This mechanism serves as a homeostatic feedback to control the activity of PABP in cells.
Keywords:
- EDD,
- translation initiation,
- ubiquitination
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