Tubulin chaperone E binds microtubules and proteasomes and protects against misfolded protein stress.
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.
Voloshin
Olga
O
Department of Life Sciences, Ben Gurion University of the Negev, P.O. Box 653, 84105, Beersheba, Israel.
Gocheva
Yana
Y
Gutnick
Marina
M
Movshovich
Natalia
N
Bakhrat
Anya
A
Baranes-Bachar
Keren
K
Bar-Zvi
Dudy
D
Parvari
Ruti
R
Gheber
Larisa
L
Raveh
Dina
D
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics* / Q000378:metabolism; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D018832:Molecular Chaperones; D011506:Proteins; D014404:Tubulin; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex