High impact information on cdc13

• The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization [1].
• The fission yeast Schizosaccharomyces pombe has a B-type cyclin, which is a nuclear protein encoded by the cdc13 gene [2].
• Here we show that srw1p is not required for the degradation of cdc13p during mitotic exit demonstrating that there are two systems operative at different stages of the cell cycle for cdc13p degradation, and that srw1p is phosphorylated by Cdk-cdc13p only becoming dephosphorylated during G(1) arrest [3].
• We propose that this phosphorylation targets srw1p for proteolysis and inhibits its activity to promote cdc13p turnover [3].
• Downregulation of cyclin-dependent kinase (Cdk)-mitotic cyclin complexes is important during cell cycle progression and in G(1) arrested cells undergoing differentiation. srw1p, a member of the Fizzy-related protein family in fission yeast, is required for the degradation of cdc13p mitotic cyclin B during G(1) arrest [3].

Biological context of cdc13

• The products of the cdc13+ and cdc2+ genes form a stable complex that displays protein kinase activity in vitro. p63cdc13 is a substrate of p34cdc2, the catalytic subunit of the kinase [1].
• Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase [4].
• These included suppression of cdc13ts alleles by introduction of the cdc2+ gene on a multi-copy plasmid vector. cdc13+ is required in G2 for mitotic initiation and was shown to play no role in the G1 phase of the cell cycle. cdc2+, however, is essential in G1 for DNA replication and in G2 for mitosis [4].
• This suppressor mutation was shown to be an allele of cdc13, a previously identified gene [4].
• When a major part of the cdc13+ gene is deleted from the chromosome, cells arrest in interphase, but partial loss of gene activity leads to cells containing condensed chromosomes, aberrant septa and a microtubular cytoskeleton with characteristics of both G2 and M [5].

Anatomical context of cdc13

• By phenotypic complementation of the cdc2 and the cdc13 mutants of the fission yeast Schizosaccharomyces pombe, we have cloned two novel multicopy suppressors from a cDNA library of the human fibroblast [6].
• The relationship between actin and cell wall deposition was further confirmed in three temperature-sensitive cell division cycle (cdc) mutants; cdc10, cdc11 and cdc13 [7].

Associations of cdc13 with chemical compounds

• (5) Experiments with the mutant cdc10-129 and with hydroxyurea show that the initial signal to begin synthesis of cdc13 originates at Start [8].

Physical interactions of cdc13

• Phosphorylation at Tyr 15 inhibits activation of the cdc2/cdc13 complex whereas phosphorylation of Thr 167 is required for kinase activity [9].

Other interactions of cdc13

• One of these, cdc13+, encodes a protein with homology to cyclin [10].
• We also show that a dramatic increase in the level of the cdc13 protein is associated with loss of suc1 [11].
• We propose that rum1p acts as an adaptor targeting cdc13p for degradation by the cyclosome [12].
• (2) cdc13 levels in wee1 cells fall to zero in interphase [8].
• We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin-associated cdc2p kinase activity and for phermone-induced G1 arrest [12].

Analytical, diagnostic and therapeutic context of cdc13

• By indirect immunofluorescence microscopy using antibodies to the appropriate bacterially-expressed protein, we have shown that both cdc13 and cdc2 are nuclear proteins in S. pombe [10].
• To clone P. carinii cdc13, degenerate polymerase chain reaction was undertaken using primers generated from amino-acid motifs conserved in fungal Cdc13 proteins [13].

References