Compartmentalization of the functions and regulation of the mitotic cyclin Clb2 in S. cerevisiae.
Orderly progression through the eukaryotic cell cycle is a complex process involving both regulation of cyclin dependent kinase activity and control of specific substrate-Cdk interactions. In Saccharomyces cerevisiae, the mitotic cyclin Clb2 has a central role in regulating the onset of anaphase and in maintaining the cellular shape of the bud by inhibiting growth polarization induced in G1. However, how Clb2 and the partially redundant cyclin Clb1 confer specificity to Cdk1 in these processes still remains unclear. Here, we show that Clb2 mutants impaired in nuclear import or export are differentially affected for subsets of Clb2 functions while remaining fully functional for others. Our data support a direct role of the cytoplasmic pool of Clb1,2-Cdk1 in terminating cytoskeleton and growth polarization, independently of G1 cyclin transcriptional regulation. By contrast, the nuclear form of the cyclin is required for timely initiation of anaphase. Clb2 localization influences its stage-specific degradation as well. We report that Clb2 trapped in the cytoplasm is stabilized during anaphase but not at the time of mitotic exit. Altogether, our results demonstrate that the subcellular localization of the mitotic cyclin Clb2 is one of the key determinants of its biological function.
Eluère
Raïssa
R
Genome Instability and Carcinogenesis, CNRS FRE 2931, 31 chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
Offner
Nicolas
N
Varlet
Isabelle
I
Motteux
Olivia
O
Signon
Laurence
L
Picard
André
A
Bailly
Eric
E
Simon
Marie-Noëlle
MN
D002451:Cell Compartmentation; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins