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Molecular and Cellular Biology, March 2008, p. 1829-1840, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01256-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Centrin/Cdc31 Is a Novel Regulator of Protein Degradation{triangledown}

Li Chen and Kiran Madura*

Department of Biochemistry, Robert Wood Johnson Medical School, SPH/RWJMS Room 383, 683 Hoes Lane, Piscataway, New Jersey 08854

Received 12 July 2007/ Returned for modification 4 September 2007/ Accepted 11 December 2007

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 by CDC31, 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, a cdc31 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.

* Corresponding author. Mailing address: Department of Biochemistry, Robert Wood Johnson Medical School, SPH/RWJMS Room 383, 683 Hoes Lane, Piscataway, NJ 08854. Phone: (732) 235-5602. Fax: (732) 235-4783. E-mail: maduraki{at}umdnj.edu

{triangledown} Published ahead of print on 26 December 2007.

Molecular and Cellular Biology, March 2008, p. 1829-1840, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01256-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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