RRC ID 11358
Author Esteban V, Sacristán M, Andrés S, Bueno A.
Title The Flp1/Clp1 phosphatase cooperates with HECT-type Pub1/2 protein-ubiquitin ligases in Schizosaccharomyces pombe.
Journal Cell Cycle
Abstract The Schizosaccharomyces pombe Flp1p serine-threonine phosphatase is required for the degradation of the mitotic inducer Cdc25p at the end of mitosis. Cdc25p degradation prevents Cdc2p-tyrosine 15 dephosphorylation and, thus, contributes to the timely inactivation of mitotic CDK-associated kinase activity. Both RING- and HECT-type protein-ubiquitin ligases are involved in Cdc25p destabilization. Flp1p function is required for Cdc25p ubiquitination via anaphase-promoting complex/cyclosome or APC/C (RING-type) and the absence of Pub1p (HECT-type) stabilizes the mitotic inducer. In the present report, we study the functional relationship of Flp1p with Pub1p and Pub2p HECT-type-protein ubiquitin ligases. We show that Flp1p is required for the rapid degradation of Cdc25p while Pub1p is responsible for the long-term destabilization of the mitotic inducer. Accordingly, flp1 and pub1 mutants have a strong genetic interaction, correlating defects in the coordination of mitosis and cytokinesis with the stabilization of hyperactive Cdc25p. However, we also show that Flp1 and Pub2p proteins functionally interact in vivo suggesting that both proteins belong to the same regulatory network in S. pombe cells. Thus Flp1p appears to have an important role in integrating HECT- and RING-type ubiquitin ligases in cell cycle control.
Volume 7(9)
Pages 1269-76
Published 2008-5-1
DOI 10.4161/cc.7.9.5947
PII 5947
PMID 18418059
MeSH Carbon-Nitrogen Ligases / genetics Carbon-Nitrogen Ligases / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cytokinesis / genetics Fungal Proteins / genetics Fungal Proteins / metabolism Gene Expression Regulation, Enzymologic / genetics Gene Expression Regulation, Fungal / genetics Genes, cdc / physiology Mitosis / genetics Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism* Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Ubiquitin-Protein Ligase Complexes / genetics Ubiquitin-Protein Ligase Complexes / metabolism* Ubiquitination / genetics ras-GRF1 / genetics ras-GRF1 / metabolism
IF 3.699
Times Cited 11