TY  - JOUR
A1  - Leznicki, Pawel
A1  - Korac-Prlic, Jelena
A1  - Kliza, Katarzyna
A1  - Husnjak, Koraljka
A1  - Nyathi, Yvonne
A1  - Đikić, Ivan
A1  - High, Stephen
T1  - Binding of SGTA to Rpn13 selectively modulates protein quality control
T2  - Journal of cell science
N2  - 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.
KW  - Bag6
KW  - Mislocalised proteins
KW  - Proteasomes
KW  - Protein degradation
KW  - TPR
KW  - Ubiquitylation
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50571
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-505710
SN  - 1477-9137
SN  - 0021-9533
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
VL  - 128
IS  - 17
SP  - 3187
EP  - 3196
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -