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Tubulin chaperone E binds microtubules and proteasomes and protects against misfolded protein stress.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2010 Jun; Vol. 67 (12), pp. 2025-38. Date of Electronic Publication: 2010 Mar 04. - Publication Year :
- 2010
-
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 alpha-tubulin and promotes alpha/beta dimerization. We show that Pac2 functions in MT dynamics: the CAP-Gly domain binds alpha-tubulin and MTs, and functions in suppression of benomyl sensitivity of pac2Delta 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. pac2Delta 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.
- Subjects :
- Amino Acid Sequence
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Cytoskeleton genetics
Cytoskeleton metabolism
Dimerization
F-Box Proteins genetics
F-Box Proteins metabolism
F-Box-WD Repeat-Containing Protein 7
Humans
Hypoparathyroidism metabolism
Intellectual Disability genetics
Intellectual Disability metabolism
Intracellular Signaling Peptides and Proteins
Microtubules genetics
Mutation
Proteasome Endopeptidase Complex genetics
Proteins genetics
Proteins metabolism
Syndrome
Tubulin genetics
Ubiquitin genetics
Ubiquitin metabolism
Ubiquitin-Protein Ligases genetics
Ubiquitin-Protein Ligases metabolism
Hypoparathyroidism genetics
Microtubules metabolism
Molecular Chaperones genetics
Molecular Chaperones metabolism
Molecular Chaperones physiology
Proteasome Endopeptidase Complex metabolism
Tubulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 67
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 20204449
- Full Text :
- https://doi.org/10.1007/s00018-010-0308-8