In CK2 inactivated cells the cyclin dependent kinase inhibitor Sic1 is involved in cell-cycle arrest before the onset of S phase.
Protein kinase CK2 is a heterotetramer composed of two catalytic and two regulatory subunits. In Saccharomyces cerevisiae the catalytic subunits (alpha and alpha') are encoded by the CKA1, CKA2 genes. cka1Deltacka2(ts) mutants arrest cell cycle in both G1 and G2/M at 37 degrees C. Hence, it has been proposed that CK2 plays an important role in cell-cycle progression and several cell-cycle proteins have been reported to be CK2 substrates. We have previously shown that Sic1, the inhibitor of Clb5-Cdc28 complexes required for the G1/S transition, is a physiologically relevant CK2 substrate. Here we show that CK2 inactivation up-regulates Sic1 level resulting in severe down-regulation of Clb5-Cdc28 kinase activity. Concurrent inactivation of Sic1 and CK2 leads to accumulation of cells with a post-synthetic DNA content and short/elongated spindles, typical of cells arrested in mitosis. These findings indicate that Sic1 plays a major role during G1 arrest of CK2-inactivated cells.
Tripodi
Farida
F
Dipartimento di Biotecnologie e Bioscienze, Università Milano-Bicocca, P.zza della Scienza 2, 20126 Milano, Italy.
Zinzalla
Vittoria
V
Vanoni
Marco
M
Alberghina
Lilia
L
Coccetti
Paola
P
D017209:Apoptosis / Q000502:physiology*; D047390:Casein Kinase II / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D016196:S Phase / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D047390:Casein Kinase II