Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell cycle in Saccharomyces cerevisiae is controlled by regulation of START in late G1. The CLN1, CLN2 and CLN3 family of cyclin homologues is required for cells to pass START. They probably act by activating the CDC28 protein kinase. Expression of CLN1 or CLN3 under the control of an inducible promoter shows that transcription of either gene is sufficient for cyclin-deficient strains arrested in G1 to traverse START. A model of START regulation involves activation of CDC28 kinase by any CLN protein, leading to activation of CLN1 and CLN2 transcription in a positive feedback loop and passage through START. The cell cycle-dependent transcriptional regulators SWI4 and SWI6 may be components of the feedback loop. Cell cycle commitment entails resistance to the inhibitory action of mating factor, which correlates with peak levels of CLN1 and CLN2 mRNAs. FAR1 encodes an alpha-factor-dependent inhibitor of CLN function whose expression is markedly reduced at the time of START. The interplay of all these factors may sharpen the START transition such that it is close to an all-or-nothing switch event. This may be important for several START-dependent events to be activated at the same time, leading to coordinated cell cycle progression.
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PMID:Is START a switch? 148 46

In rapidly growing cells of the budding yeast Saccharomyces cerevisiae, the cell cycle is regulated chiefly at Start, just before the G1-S boundary, whereas in the fission yeast Schizosaccharomyces pombe, the cycle is predominantly regulated at G2-M. Both control points are present in both yeasts, and both require the p34cdc2 protein kinase. At G2-M, p34cdc2 kinase activity in S. pombe requires a B-type cyclin in a complex with p34cdc2; this complex is the same as MPF (maturation promoting factor). The p34cdc2 activity at the G1-S transition in S. cerevisiae may be regulated by a similar cyclin complex, using one of the products of a new class of cyclin genes (CLN1, CLN2 and WHI1 (DAF1/CLN3)). At least one is required for progression through the G1-S phase, and deletion of all three leads to G1 arrest. WHI1 was isolated as a dominant allele causing budding yeast cells to divide at a reduced size and was later independently identified as DAF1, a dominant allele of which rendered the cells refractory to the G1-arrest induced by the mating pheromone alpha-factor. The dominant alleles are truncations thought to yield proteins of increased stability, and the cells are accelerated through G1. Without WHI1 function, the cells are hypersensitive to alpha-factor, enlarged and delayed in G1. Heretofore, this G1-class of cyclins has not been identified in other organisms. We have isolated a G1-type cyclin gene called puc1+ from S. pombe, using a functional assay in S. cerevisiae. Expression of puc1+ in S. pombe indicates that it has a cyclin-like role in the fission yeast distinct from the role of the B-type mitotic cyclin.
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PMID:Identification of a G1-type cyclin puc1+ in the fission yeast Schizosaccharomyces pombe. 182 91

Yeast cells become committed to the mitotic cell cycle at a stage during G1 called Start. To enter Start, cells must grow to a critical size. They also require the CDC28 protein kinase and at least one of three G1-specific cyclins encoded by CLN1, 2, and 3. It is thought that Start is triggered by the accumulation of G1 cyclins that bind to the CDC28 kinase and activate it. So what determines the accumulation of G1 cyclins? For CLN1 and CLN2, transcriptional activation could be involved because their RNAs appear transiently during the cell cycle as cells undergo Start. Here we report that the appearance of CLN1 and CLN2 RNAs depends on an active CDC28 kinase and is stimulated by CLN3 activity. We propose that CDC28 kinase activity due to CLN1 and CLN2 proteins arises through a positive feedback loop which allows CLN proteins to promote their own synthesis.
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PMID:Positive feedback in the activation of G1 cyclins in yeast. 182 7

Entry into the mitotic cycle (START) requires a protein kinase encoded by the CDC28 gene and one of three redundant G1-specific cyclins encoded by CLN1, -2, and -3. SWI4 and SWI6 are transcription factors required for the START-dependent activation of the HO endonuclease gene. They also fulfill an overlapping but essential role for cell division since cells deleted for both genes are inviable. We show that the essential role of SWI4 and SWI6 is to ensure the activity of G1-specific cyclin genes. SWI4 and SWI6 appear necessary for the transcription of CLN1 and CLN2, but not for that of CLN3. CLN3 function is, however, also dependent on SWI4 and SWI6.
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PMID:The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast. 183 38

FUS3 is functionally redundant with KSS1, a homologous yeast protein kinase, for a step(s) in signal transduction between the beta subunit of the guanine nucleotide binding protein (G protein), STE4, and the mating type-specific transcriptional activator, STE12. Either FUS3 or KSS1 can execute this function; when neither gene encoding these protein kinases is present, signal transduction is blocked, causing sterility. This functional redundancy is strain dependent; some standard laboratory strains (S288C) are kss1-. FUS3 has additional functions required for cell cycle arrest and vegetative growth that do not overlap with KSS1 functions. FUS3 mediates cell cycle arrest during mating through transcriptional repression of two G1 cyclins (CLN1 and CLN2) and through posttranscriptional inhibition of a third G1 cyclin (CLN3). FUS3 is also required for vegetative growth in haploid strains dependent upon CLN3 for cell cycle progression but is not required in strains dependent upon either CLN1 or CLN2, suggesting a functional divergence among the three G1 cyclins. The diverse roles for FUS3 suggest that the FUS3 protein kinase has multiple substrates, some of which may be shared with KSS1.
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PMID:FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction. 194 50

The S. cerevisiae CLN genes encode cyclin homologs essential for progression from G1 to S phase. The CLN2 gene encodes a 62 kd polypeptide that accumulates periodically, peaking during G1 and decreasing rapidly thereafter, and is rapidly lost following exposure of cells to mating pheromone. Cln2 abundance can be explained by the G1-specific accumulation of the CLN2 transcript coupled with instability of the Cln2 protein. The abundance of the CLN1 and CLN2 transcripts increases greater than 5-fold during the G1 interval, decreasing dramatically as cells enter S phase. Both transcripts decrease in cells responding to mating pheromone. Finally, we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex. This physical interaction is consistent with the genetic interaction between the CLN genes and CDC28 and suggests that Cln proteins are an essential component of the active protein kinase complex required for the G1 to S transition.
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PMID:G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase. 214 20

Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28, which encodes a protein kinase involved in control of cell division. CLN1 and CLN2 encode closely related proteins that also share homology with cyclins. Cyclins, characterized by a dramatic periodicity of abundance through the cell cycle, are thought to be involved in mitotic induction in animal cells. A dominant mutation in the CLN2 gene, CLN2-1, advances the G1- to S-phase transition in cycling cells and impairs the ability of cells to arrest in G1 phase in response to external signals, suggesting that the encoded protein is involved in G1 control of the cell cycle in Saccharomyces.
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PMID:A family of cyclin homologs that control the G1 phase in yeast. 256 41

Cyclins were discovered in marine invertebrates based on their dramatic cell cycle periodicity. Recently, the products of three genes associated with cell cycle progression in S. cerevisiae were found to share limited homology with cyclins. Mutational elimination of the CLN1, CLN2, and DAF1/WHI1 products leads to cell cycle arrest independent of cell type, while expression of any one of the genes allows cell proliferation. Using strains where CLN1 was expressed conditionally, the essential function of Cln proteins was found to be limited to the G1 phase. Furthermore, the ability of the Cln proteins to carry out this function was found to decay rapidly upon cessation of Cln biosynthesis. The data are consistent with the hypothesis that Cln proteins activate the Cdc28 protein kinase, shown to be essential for the G1 to S phase transition in S. cerevisiae. Because of the apparent functional redundancy of these genes, DAF1/WHI1 has been renamed CLN3.
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PMID:An essential G1 function for cyclin-like proteins in yeast. 257 33

In the interest of identifying components of the Cdc28 protein kinase complex, dosage suppression analysis was performed on temperature-sensitive and dominant negative CDC28 mutations. Dosage suppression is based on a rationale in which elevated expression of wild-type genes can rescue mutations in a target gene as a result of interaction between the respective encoded proteins. Three sequences capable of rescuing a temperature sensitive cdc28 mutation were isolated from a library of wild-type genomic DNA segments in the high copy vector YEp13. Two of these, named CLN1 and CLN2 were found to encode closely related proteins with homology to cyclins. The third, CKS1, encodes an 18K (K = 10(3) Mr) protein that has been shown to be a component of the Cdc28 protein kinase complex and is a homolog of the suc1+ product of fission yeast. A number of dosage suppressors of the CDC28-dn1 dominant negative mutation have been isolated. The one analyzed to date encodes a truncated subunit of the mitochondrial enzyme succinyl-CoA synthetase. The basis for suppression in this case remains to be elucidated.
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PMID:Analysis of the Cdc28 protein kinase complex by dosage suppression. 269 37

In budding yeast G1 cells increase in cell mass until they reach a critical cell size, at which point (called Start) they enter S phase, bud and duplicate their spindle pole bodies. Activation of the Cdc28 protein kinase by G1-specific cyclins Cln1, Cln2 or Cln3 is necessary for all three Start events. Transcriptional activation of CLN1 and CLN2 by SBF and MBF transcription factors also requires an active Cln-Cdc28 kinase and it has therefore been proposed that the sudden accumulation of CLN1 and CLN2 transcripts during late G1 occurs via a positive feedback loop. We report that whereas Cln1 and Cln2 are required for the punctual execution of most, if not all, other Start-related events, they are not required for the punctual activation of SBF- or MBF-driven transcription. Cln3, on the other hand, is essential. By turning off cyclin B proteolysis and turning on proteolysis of the cyclin B-Cdc28 inhibitor p40SIC1, Cln1 and Cln2 kinases activate cyclin B-Cdc28 kinases and thereby trigger S phase. Thus the accumulation of Cln1 and Cln2 kinases which starts the yeast cell cycle is set in motion by prior activation of SBF- and MBF-mediated transcription by Cln3-Cdc28 kinase. This dissection of regulatory events during late G1 demands a rethinking of Start as a single process that causes cells to be committed to the mitotic cell cycle.
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PMID:Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. 758 10


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