The Saccharomyces cerevisiae ubiquitin-proteasome system.
Our studies of the yeast ubiquitin-proteasome pathway have uncovered a number of general principles that govern substrate selectivity and proteolysis in this complex system. Much of the work has focused on the destruction of a yeast transcription factor, MAT alpha 2. The alpha 2 protein is polyubiquitinated and rapidly degraded in alpha-haploid cells. One pathway of proteolytic targeting, which depends on two distinct endoplasmic reticulum-localized ubiquitin-conjugating enzymes, recognizes the hydrophobic face of an amphipathic helix in alpha 2. Interestingly, degradation of alpha 2 is blocked in a/alpha-diploid cells by heterodimer formation between the alpha 2 and a1 homeodomain proteins. The data suggest that degradation signals may overlap protein-protein interaction surfaces, allowing a straightforward steric mechanism for regulated degradation. Analysis of alpha 2 degradation led to the identification of both 20S and 26S proteasome subunits, and several key features of proteasome assembly and active-site formation were subsequently uncovered. Finally, it has become clear that protein (poly) ubiquitination is highly dynamic in vivo, and our studies of yeast de-ubiquitinating enzymes illustrate how such enzymes can facilitate the proteolysis of diverse substrates.
Hochstrasser
M
M
Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637, USA. hocl@midway.uchicago.edu
Johnson
P R
PR
Arendt
C S
CS
Amerik AYu
Swaminathan
S
S
Swanson
R
R
Li
S J
SJ
Laney
J
J
Pals-Rylaarsdam
R
R
Nowak
J
J
Connerly
P L
PL
D000595:Amino Acid Sequence; D001704:Biopolymers / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D019751:Intramolecular Transferases; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins / Q000378:metabolism*
D001704:Biopolymers; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D025821:Polyubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D019751:Intramolecular Transferases; C068903:DEG1 protein, S cerevisiae