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

Authors

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

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

Copyright information

© Springer Basel AG 2010