Open AccessCentrin/Cdc31 Is a Novel Regulator of Protein Degradation
Author(s) -
Li Chen,
Kiran Madura
Publication year - 2008
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01256-07
Subject(s) - biology , nucleotide excision repair , xeroderma pigmentosum , ddb1 , saccharomyces cerevisiae , dna repair , protein degradation , dna binding protein , dna damage , proteasome , microbiology and biotechnology , mutant , cell cycle protein , ubiquitin , dna , replication protein a , ef hand , biochemistry , peptide sequence , ubiquitin ligase , yeast , gene , cell cycle , transcription factor
Rad23 is required for efficient protein degradation and performs an important role in nucleotide excision repair.Saccharomyces cerevisiae Rad23, and its human counterpart (hHR23), are present in a complex containing the DNA repair factor Rad4 (termed XPC, for xeroderma pigmentosum group C, in humans). XPC/hHR23 was also reported to bind centrin-2, a member of the superfamily of calcium-binding EF-hand proteins. We report here that yeast centrin, which is encoded byCDC31 , is similarly present in a complex with Rad4/Rad23 (called NEF2). The interaction between Cdc31 and Rad23/Rad4 varied by growth phase and reflected oscillations in Cdc31 levels. Strikingly, acdc31 mutant that formed a weaker interaction with Rad4 showed sensitivity to UV light. Based on the dual function of Rad23, in both DNA repair and protein degradation, we questioned if Cdc31 also participated in protein degradation. We report here that Cdc31 binds the proteasome and multiubiquitinated proteins through its carboxy-terminal EF-hand motifs. Moreover,cdc31 mutants were highly sensitive to drugs that cause protein damage, failed to efficiently degrade proteolytic substrates, and formed altered interactions with the proteasome. These findings reveal for the first time a new role for centrin/Cdc31 in protein degradation.