Binding of SGTA to Rpn13 selectively modulates protein quality control

Leznicki, P. and Korac-Prlic, J. and Kliza, K. and Husnjak, K. and Nyathi, Y. and Dikic, I. and High, S. (2015) Binding of SGTA to Rpn13 selectively modulates protein quality control. Journal of Cell Science, 128 (17). pp. 3187-3196. ISSN 0021-9533

Full content URL: http://dx.doi.org/10.1242/jcs.165209

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Abstract

Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation.

Keywords:Bag6, Mislocalised proteins, Proteasomes, Protein degradation, TPR, Ubiquitylation, JCOpen
Subjects:C Biological Sciences > C130 Cell Biology
Divisions:College of Science > School of Life Sciences
ID Code:27025
Deposited On:21 Jun 2017 08:20

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