Disease relevance of pas1

• Mutations in cut4 result in hypersensitivity to cyclic AMP and to stress-inducing heavy metals, inhibition of the onset of anaphase, disruption of the 20S complex, and inhibition of mitotic cyclin ubiquitination [1].

High impact information on pas1

• Thus, ORC bound mitotic Cyclin B/Cdc2 kinase imposes the dependency of S phase on an intervening mitosis but not the temporal licensing of replication origins between each S phase [2].
• Stable association of mitotic cyclin B/Cdc2 to replication origins prevents endoreduplication [2].
• We show here that the state of the p34cdc2-p56cdc13 mitotic B cyclin complex determines whether a fission yeast cell undergoes S phase or mitosis [3].
• The cig1+ protein has a "cyclin box" approximately 40% identical to B-type cyclins of other species, but lacks the "destruction box" required for proteolysis of mitotic cyclins [4].
• In Schizosaccharomyces pombe, the onset of mitosis is determined by activation of a complex of the p34cdc2 protein kinase and a cyclin protein that is specific to the G2 phase of the cell cycle [5].

Biological context of pas1

• A pcl-like cyclin activates the Res2p-Cdc10p cell cycle "start" transcriptional factor complex in fission yeast [6].
• Activation of the protein kinase also requires the cyclin homolog p56cdc13, which also functions post activation at a later stage of mitosis [7].
• In most species, including the fission yeast Schizosaccharomyces pombe, the Cdc2/cyclin B mitosis-inducing kinase is maintained in an inhibited state during interphase as a result of phosphorylation of a tyrosine residue in the ATP-binding region of Cdc2 (refs 1-3) [8].
• Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase [9].
• The 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction and sister chromatid separation [1].

Anatomical context of pas1

• These results suggest a key regulatory role of the cdc2-cyclin complex in the initiation of mitotic spindle formation and also that mitotic microtubule function is required for cdc2 activation [10].
• That they participate in the G2-M transition is supported by the fact that when synthetic cyclin messenger RNAs from clam and sea urchin are microinjected into the G2-arrested oocytes of Xenopus, they induce maturation [11].
• Cytokinesis in eukaryotic cells requires the inactivation of mitotic cyclin-dependent kinase complexes [12].

Associations of pas1 with chemical compounds

• Disruption of pas1+ causes defects in arginine and leucine uptake that are remarkably similar to Deltatsc1 and Deltatsc2, whereas Deltapas1Deltatsc1 and Deltapas1Deltatsc2 double mutants have more severe amino acid uptake defects [13].
• The association of cyclin and p34cdc2 is not sufficient for activation of cdc2 kinase, however; dephosphorylation of key tyrosine and threonine residues of p34cdc2 is necessary to turn on its kinase activity [9].
• We identified a truncated allele of dam1 as a multicopy suppressor of the sensitivity of cdc13-117 (cyclin B) and mal3-1 (EB-1) cells to thiabendazole, a microtubule poison [14].
• However, little is known about how cyclic AMP interacts with the central cell cycle machinery, Cdc2, the cyclin-dependent kinase that induces mitosis [15].
• Cyclin C and the cyclin C-dependent protein kinase are associated with the RNA polymerase II Mediator complex, which regulates initiation of transcription in response to signals from activators and repressors bound to upstream promoter elements [16].

Physical interactions of pas1

• During interphase the cdc2/cyclin complex is assembled in an inactive state that requires cdc25+ gene function for M-phase activation [17].

Regulatory relationships of pas1

• Treatment of cells with the antimicrotubule drug thiabendazole prevents cyclin degradation and blocks the tyrosine dephosphorylation and activation of cdc2 [10].

Other interactions of pas1

• We have recently isolated the pas1(+) gene as a multicopy suppressor of the res1 null mutant [6].
• This is due to the fact that destruction of mitotic cyclin and Cut2 in the nucleus is dramatically delayed, though polyubiquitination of Cdc13 occurs in cut8 mutant [18].
• The puc1+ gene, encoding a G1-type cyclin from the fission yeast Schizosaccharomyces pombe, was originally isolated by complementation in the budding yeast Saccharomyces cerevisiae [19].
• One of these, cdc13+, encodes a protein with homology to cyclin [20].
• Distinct nuclear and spindle pole body population of cyclin-cdc2 in fission yeast [10].

Analytical, diagnostic and therapeutic context of pas1

• The cellular distribution of the fission yeast mitotic cyclin B, p63cdc13, was investigated by a combination of indirect immunofluorescence light microscopy, immunogold electron microscopy, and nuclear isolation and fractionation [21].
• Therefore, as observed by immunofluorescence in other systems, it seems that cyclin subunits target p34cdc2 to specific cellular sites and this is certainly important for its function [22].
• It is becoming increasingly clear that the inactivation of the mitosis-promoting cyclin-dependent kinase, which marks the completion of the nuclear division cycle, is essential for actomyosin ring constriction and division septum assembly in both yeasts [23].

References