Binding of SGTA to Rpn13 selectively modulates protein quality control

Pawel Leznicki, Jelena Korac-Prlic, Katarzyna Kliza, Koraljka Husnjak, Yvonne Nyathi, Ivan Dikic, Stephen High (Lead / Corresponding author)

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 SGTATPR 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.

Original languageEnglish
Pages (from-to)3187-3196
Number of pages10
JournalJournal of Cell Science
Volume128
Issue number17
DOIs
Publication statusPublished - 1 Sep 2015

Fingerprint

Quality Control
Membrane Proteins
Proteasome Endopeptidase Complex
Proteins
Ubiquitin
Point Mutation
Peptides

Keywords

  • Bag6
  • Mislocalised proteins
  • Proteasomes
  • Protein degradation
  • TPR
  • Ubiquitylation

Cite this

Leznicki, P., Korac-Prlic, J., Kliza, K., Husnjak, K., Nyathi, Y., Dikic, I., & High, S. (2015). Binding of SGTA to Rpn13 selectively modulates protein quality control. Journal of Cell Science, 128(17), 3187-3196. https://doi.org/10.1242/jcs.165209
Leznicki, Pawel ; Korac-Prlic, Jelena ; Kliza, Katarzyna ; Husnjak, Koraljka ; Nyathi, Yvonne ; Dikic, Ivan ; High, Stephen. / Binding of SGTA to Rpn13 selectively modulates protein quality control. In: Journal of Cell Science. 2015 ; Vol. 128, No. 17. pp. 3187-3196.
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Leznicki, P, Korac-Prlic, J, Kliza, K, Husnjak, K, Nyathi, Y, Dikic, I & High, S 2015, 'Binding of SGTA to Rpn13 selectively modulates protein quality control', Journal of Cell Science, vol. 128, no. 17, pp. 3187-3196. https://doi.org/10.1242/jcs.165209

Binding of SGTA to Rpn13 selectively modulates protein quality control. / Leznicki, Pawel; Korac-Prlic, Jelena; Kliza, Katarzyna; Husnjak, Koraljka; Nyathi, Yvonne; Dikic, Ivan; High, Stephen (Lead / Corresponding author).

In: Journal of Cell Science, Vol. 128, No. 17, 01.09.2015, p. 3187-3196.

Research output: Contribution to journalArticle

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Leznicki P, Korac-Prlic J, Kliza K, Husnjak K, Nyathi Y, Dikic I et al. Binding of SGTA to Rpn13 selectively modulates protein quality control. Journal of Cell Science. 2015 Sep 1;128(17):3187-3196. https://doi.org/10.1242/jcs.165209