Cpc2, a fission yeast homologue of mammalian RACK1 protein, interacts withRan1 (Pat1) kinase to regulate cell cycle progression and meiotic development

Citation
M. Mcleod et al., Cpc2, a fission yeast homologue of mammalian RACK1 protein, interacts withRan1 (Pat1) kinase to regulate cell cycle progression and meiotic development, MOL CELL B, 20(11), 2000, pp. 4016-4027
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR AND CELLULAR BIOLOGY
ISSN journal
0270-7306 → ACNP
Volume
20
Issue
11
Year of publication
2000
Pages
4016 - 4027
Database
ISI
SICI code
0270-7306(200006)20:11<4016:CAFYHO>2.0.ZU;2-H
Abstract
The Schizosaccharomyces pombe ran1/pat1 gene regulates the transition betwe en mitosis and meiosis. Inactivation of Ran1 (Pat1) kinase is necessary and sufficient for cells to exit the cell cycle and undergo meiosis. The yeast two-hybrid interaction trap was used to identify protein partners for Ran1 /Pat1. Here we report the identification of one of these, Cpc2. Cpc2 encode s a homologue of RACK1, a WD protein with homology to the beta subunit of h eterotrimeric G proteins. RACK1 is a highly conserved protein, although its function remains undefined. In mammalian cells, RACK1 physically associate s with some signal transduction proteins, including Src and protein kinase C. Fission yeast cells containing a cpa null allele are viable but cell cyc le delayed. cpc2 Delta cells fail to accumulate in G(1) when starved of nit rogen. This leads to defects in conjugation and meiosis. Copurification stu dies show that although Cpc2 and Ran1 (Pat1) physically associate, Cpc2 doe s not alter Ran1 (Pat1) kinase activity in vitro. Using a Ran1 (Pat1) fusio n to green fluorescent protein, we show that localization of the kinase is impaired in cpc2 Delta cells. Thus, in parallel with the proposed role of R ACK1 in mammalian cells, fission yeast cpc2 may function as an anchoring pr otein for Ran1 (Pat1) kinase. All defects associated with loss of cpc2 are reversed in cells expressing mammalian RACK1, demonstrating that the fissio n yeast and mammalian gene products are indeed functional homologues.