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PMID: 10921876 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

APC(ste9/srw1) promotes degradation of mitotic cyclins in G(1) and is inhibited by cdc2 phosphorylation.

The EMBO journal ·Vol. 19 ·No. 15 ·2000-08-01 ·Pages 3945-55

Blanco MA, Sánchez-Díaz A, de Prada JM, Moreno S

Abstract

Fission yeast ste9/srw1 is a WD-repeat protein highly homologous to budding yeast Hct1/Cdh1 and Drosophila Fizzy-related that are involved in activating APC/C (anaphase-promoting complex/cyclosome). We show that APC(ste9/srw1) specifically promotes the degradation of mitotic cyclins cdc13 and cig1 but not the S-phase cyclin cig2. APC(ste9/srw1) is not necessary for the proteolysis of cdc13 and cig1 that occurs at the metaphase-anaphase transition but it is absolutely required for their degradation in G(1). Therefore, we propose that the main role of APC(ste9/srw1) is to promote degradation of mitotic cyclins when cells need to delay or arrest the cell cycle in G(1). We also show that ste9/srw1 is negatively regulated by cdc2-dependent protein phosphorylation. In G(1), when cdc2-cyclin kinase activity is low, unphosphorylated ste9/srw1 interacts with APC/C. In the rest of the cell cycle, phosphorylation of ste9/srw1 by cdc2-cyclin complexes both triggers proteolysis of ste9/srw1 and causes its dissociation from the APC/C. This mechanism provides a molecular switch to prevent inactivation of cdc2 in G(2) and early mitosis and to allow its inactivation in G(1).

MeSH Terms
Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome CDC2 Protein Kinase/metabolism Cell Cycle Proteins/metabolism Cell Differentiation Conserved Sequence Cyclin B/metabolism Cyclins/metabolism Drosophila Proteins Fungal Proteins/metabolism G1 Phase/physiology Ligases/metabolism Phosphorylation Protein Binding Protein Kinases/metabolism Schizosaccharomyces/cytology Schizosaccharomyces pombe Proteins Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases
Chemicals
Cell Cycle Proteins Cig1 protein, S pombe CycB protein, Drosophila Cyclin B Cyclins Drosophila Proteins Fungal Proteins Schizosaccharomyces pombe Proteins srw1 protein, S pombe Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases Protein Kinases CDC2 Protein Kinase Ligases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Blanco M A
Instituto de Microbiología Bioquímica, Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Sánchez-Díaz A
de Prada J M
Moreno S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.15.3945
Published
2000-08-01
Pages
3945-55
Language
English
Region
England
NLM ID
8208664
PMCID
PMC306614
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.15.3945 PMC Full Text View journal details
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