title: Paip1, an effective stimulator of translation initiation, is targeted by WWP2 for ubiquitination and degradation.
abstract: Poly(A)-binding protein-interacting protein 1 (Paip1) stimulates translational initiation by inducing the circularization of mRNA. However, the mechanisms underlying Paip1 regulation, particularly its protein stability, are still unclear. Here, we show that the E6AP carboxyl terminus (HECT)-type ubiquitin ligase WW domain-containing protein 2 (WWP2), a homolog of the HECT-type ubiquitin ligase WWP1, interacts with and targets Paip1 for ubiquitination and proteasomal degradation. Mapping of the region including the WW domain of WWP2 revealed the interaction between WWP2 and the PABP-binding motif 2 (PAM2) of Paip1. The two consecutive PXXY motifs in PAM2 are required for WWP2-mediated ubiquitination and degradation. Furthermore, ectopic expression of WWP2 decreases translational stimulatory activity with the degradation of Paip1. We therefore provide evidence that the stability of Paip1 can be regulated by ubiquitin-mediated degradation, thus highlighting the importance of WWP2 as a suppressor of translation.
authors.affiliation: Department of Breast Surgery, QiLu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, QiLu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, QiLu Hospital of Shandong University, Jinan, Shandong, China sdgaohd@163.com.
authors.forename: Haidong
authors.initials: H
authors.lastname: Gao
mesh_terms: D020816:Amino Acid Motifs; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C111580:PAIP1 protein, human; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; C465283:WWP2 protein, human; D044767:Ubiquitin-Protein Ligases