Regulation of the G1 phase of the cell cycle by periodic stabilization and degradation of the p25rum1 CDK inhibitor.

作者: Javier Benito , Cristina Martín‐Castellanos , Sergio Moreno

DOI: 10.1093/EMBOJ/17.2.482

关键词: MitosisCDC2 Protein KinaseCDK inhibitorCell biologyCell cycleAnaphaseCyclinBiologyProteasomeCyclin-dependent kinase

摘要: In fission yeast, the cyclin‐dependent kinase (CDK) inhibitor p25 rum1 is a key regulator of progression through G 1 phase cell cycle. We show here that protein levels are sharply periodic. begins to accumulate at anaphase, persists in and destroyed during S phase. stabilized polyubiquitinated mutant defective 26S proteasome, suggesting its degradation normally occurs ubiquitin‐dependent proteasome pathway. Phosphorylation by cdc2–cyclin complexes residues T58 T62 important target for degradation. Mutation one or both these alanine causes stabilization induces cycle delay polyploidization due occasional re‐initiation DNA replication before mitosis. The CDK–cyclin complex cdc2–cig1, which insensitive inhibition, seems be main phosphorylates . 2 serves as trigger proteolysis. Thus, periodic accumulation CDK plays role setting threshold cyclin determining length pre‐Start ensuring correct order events.

参考文章(107)
Colin Gordon, Gordon McGurk, Mairi Wallace, Nicholas D. Hastie, A Conditional Lethal Mutant in the Fission Yeast 26 S Protease Subunit mts3 Is Defective in Metaphase to Anaphase Transition Journal of Biological Chemistry. ,vol. 271, pp. 5704- 5711 ,(1996) , 10.1074/JBC.271.10.5704
Andrew W. Murray, Marc W. Kirschner, Cyclin synthesis drives the early embryonic cell cycle. Nature. ,vol. 339, pp. 275- 280 ,(1989) , 10.1038/339275A0
Matthias Peter, Anton Gartner, Joe Horecka, Gustav Ammerer, Ira Herskowitz, FAR1 links the signal transduction pathway to the cell cycle machinery in yeast Cell. ,vol. 73, pp. 747- 760 ,(1993) , 10.1016/0092-8674(93)90254-N
Susan L. Forsburg, Paul Nurse, Identification of a Gl-type cyclin puc1 + in the fission yeast Schizosaccharomyces pombe Nature. ,vol. 351, pp. 245- 248 ,(1991) , 10.1038/351245A0
Daniel Fisher, Paul Nurse, Cyclins of the fission yeast Schizosaccharomyces pombe Seminars in Cell Biology. ,vol. 6, pp. 73- 78 ,(1995) , 10.1016/1043-4682(95)90003-9
Thomas J. Kelly, G.Steven Martin, Susan L. Forsburg, Robert J. Stephen, Alicia Russo, Paul Nurse, The fission yeast cdc18+ gene product couples S phase to START and mitosis Cell. ,vol. 74, pp. 371- 382 ,(1993) , 10.1016/0092-8674(93)90427-R
Andrew R Willems, Stefan Lanker, E.Elizabeth Patton, Karen L Craig, Timothy F Nason, Neal Mathias, Ryuji Kobayashi, Curt Wittenberg, Mike Tyers, Cdc53 Targets Phosphorylated G1 Cyclins for Degradation by the Ubiquitin Proteolytic Pathway Cell. ,vol. 86, pp. 453- 463 ,(1996) , 10.1016/S0092-8674(00)80118-X
Kim Nasmyth, At the heart of the budding yeast cell cycle Trends in Genetics. ,vol. 12, pp. 405- 412 ,(1996) , 10.1016/0168-9525(96)10041-X