Cellular and Molecular Life Sciences

, Volume 67, Issue 12, pp 2025–2038

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 Article

DOI: 10.1007/s00018-010-0308-8

Cite this article as:
Voloshin, O., Gocheva, Y., Gutnick, M. et al. Cell. Mol. Life Sci. (2010) 67: 2025. doi:10.1007/s00018-010-0308-8

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.

Keywords

Pac2CAP-GlyUbiquitin-like domainRpn1Rpn10ProteasomeTBCE

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Olga Voloshin
    • 1
  • Yana Gocheva
    • 1
  • Marina Gutnick
    • 1
  • Natalia Movshovich
    • 2
  • Anya Bakhrat
    • 1
  • Keren Baranes-Bachar
    • 1
  • Dudy Bar-Zvi
    • 1
  • Ruti Parvari
    • 3
  • Larisa Gheber
    • 2
  • Dina Raveh
    • 1
  1. 1.Department of Life SciencesBen Gurion University of the NegevBeershebaIsrael
  2. 2.Department of Clinical BiochemistryBen Gurion University of the NegevBeershebaIsrael
  3. 3.National Institute of Biotechnology Negev and Department of Virology and Developmental GeneticsFaculty of Health Sciences, Ben Gurion University of the NegevBeershebaIsrael