Tubulin chaperone e binds microtubules and proteasomes and protects against misfolded protein stress

Olga Voloshin, Yana Gocheva, Marina Gutnick, Natalia Movshovich, Anya Bakhrat, Keren Baranes-Bachar, Dudy Bar-Zvi, Ruti Parvari, Larisa Gheber, Dina Raveh

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Mutation of tubulin chaperone E (TBCE) underlies hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome with defective microtubule (MT) cytoskeleton. TBCE/yeast Pac2 comprises CAP-Gly, LRR (leucine-rich region), and UbL (ubiquitin-like) domains. TBCE folds α-tubulin and promotes α/β dimerization. We show that Pac2 functions in MT dynamics: the CAP-Gly domain binds α-tubulin and MTs, and functions in suppression of benomyl sensitivity of pac2Δ mutants. Pac2 binds proteasomes: the LRR binds Rpn1, and the UbL binds Rpn10; the latter interaction mediates Pac2 turnover. The UbL also binds the Skp1-Cdc53-F-box (SCF) ubiquitin ligase complex; these competing interactions for the UbL may impact on MT dynamics. pac2Δ mutants are sensitive to misfolded protein stress. This is suppressed by ectopic PAC2 with both the CAP-Gly and UbL domains being essential. We propose a novel role for Pac2 in the misfolded protein stress response based on its ability to interact with both the MT cytoskeleton and the proteasomes.

Original languageEnglish
Pages (from-to)2025-2038
Number of pages14
JournalCellular and Molecular Life Sciences
Volume67
Issue number12
DOIs
StatePublished - 1 Jun 2010

Keywords

  • CAP-Gly
  • Pac2
  • Proteasome
  • Rpn1
  • Rpn10
  • TBCE
  • Ubiquitin-like domain

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