A multimeric assembly factor controls the formation of alternative 20S proteasomes

被引:122
作者
Kusmierczyk, Andrew R. [1 ]
Kunjappu, Mary J. [1 ]
Funakoshi, Minoru [1 ]
Hochstrasser, Mark [1 ]
机构
[1] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
关键词
D O I
10.1038/nsmb.1389
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The proteasome is the central regulatory protease of eukaryotic cells. Heteroheptameric alpha-subunit and beta-subunit rings stack to form the 20S proteasome, which associates with a 19S regulatory particle (RP). Here we show that two yeast proteins, Pba3 and Pba4, form a previously unidentified 20S proteasome-assembly chaperone. Pba3-Pba4 interacts genetically and physically with specific proteasomal alpha subunits, and loss of Pba3-Pba4 causes both a reduction and a remodeling of cellular proteasomes. Notably, mutant cells accumulate proteasomes in which a second copy of the alpha 4 subunit replaces alpha 3. 20S proteasome-assembly defects also are associated with altered RP assembly; this unexpected result suggests that the 20S proteasome can function as an RP-assembly factor in vivo. Our data demonstrate that Pba3-Pba4 orchestrates formation of a specific type of proteasome, the first example of a trans-acting factor that controls assembly of alternative proteasomal complexes.
引用
收藏
页码:237 / 244
页数:8
相关论文
共 37 条
[31]   Membrane and soluble substrates of the Doa10 ubiquitin ligase are degraded by distinct pathways [J].
Ravid, T ;
Kreft, SG ;
Hochstrasser, M .
EMBO JOURNAL, 2006, 25 (03) :533-543
[32]  
Rivett AJ, 2001, BIOCHIMIE, V83, P363
[33]   The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle [J].
Schmidt, M ;
Haas, W ;
Crosas, B ;
Santamaria, PG ;
Gygi, SP ;
Walz, T ;
Finley, D .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2005, 12 (04) :294-303
[34]   Regulated protein degradation [J].
Varshavsky, A .
TRENDS IN BIOCHEMICAL SCIENCES, 2005, 30 (06) :283-286
[35]   Plasticity in eucaryotic 20S proteasome ring assembly revealed by a subunit deletion in yeast [J].
Velichutina, I ;
Connerly, PL ;
Arendt, CS ;
Li, X ;
Hochstrasser, M .
EMBO JOURNAL, 2004, 23 (03) :500-510
[36]   Proteasomal proteomics: Identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes [J].
Verma, R ;
Chen, S ;
Feldman, R ;
Schieltz, D ;
Yates, J ;
Dohmen, T ;
Deshaies, RJ .
MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (10) :3425-3439
[37]  
Yuan XQ, 1996, GENETICS, V144, P147