Yeast Ran-binding protein Yrb1p is required for efficient proteolysis of cell cycle regulatory proteins Pds1p and Sic1p.
Ubiquitin-dependent proteolysis of specific target proteins is required for several important steps during the cell cycle. Degradation of such proteins is strictly cell cycle-regulated and triggered by two large ubiquitin ligases, termed anaphase-promoting complex (APC) and Skp1/Cullin/F-box complex (SCF). Here we show that yeast Ran-binding protein 1 (Yrb1p), a predominantly cytoplasmic protein implicated in nucleocytoplasmic transport, is required for cell cycle regulated protein degradation. Depletion of Yrb1p results in the accumulation of unbudded G(1) cells and of cells arrested in mitosis implying a function of Yrb1p in the G(1)/S transition and in the progression through mitosis. Temperature-sensitive yrb1-51 mutants are defective in APC-mediated degradation of the anaphase inhibitor protein Pds1p and in degradation of the cyclin-dependent kinase inhibitor Sic1p, a target of SCF. Thus, Yrb1p is crucial for efficient APC- and SCF-mediated proteolysis of important cell cycle regulatory proteins. We have identified the UBS1 gene as a multicopy suppressor of yrb1-51 mutants. Ubs1p is a nuclear protein, and its deletion is synthetic lethal with a yrb1-51 mutation. Interestingly, UBS1 was previously identified as a multicopy suppressor of cdc34-2 mutants, which are defective in SCF activity. We suggest that Ubs1p may represent a link between nucleocytoplasmic transport and ubiquitin ligase activity.
Bäumer
M
M
Institute of Microbiology and Genetics, Georg-August-University, Grisebachstrasse 8, D-37077 Göttingen, Germany.
Künzler
M
M
Steigemann
P
P
Braus
G H
GH
Irniger
S
S
D000705:Anaphase; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000502:physiology; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D005947:Glucose; D005690:Galactose