Control of the yeast cell cycle is associated with assembly/disassembly of the Cdc28 protein kinase complex

Wittenberg, Curt; Reed, Steven I.

doi:10.1016/0092-8674(88)90121-3

Cited by 150 publications

(90 citation statements)

References 32 publications

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“…Passage through START requires the activation of the Cdc28 gene [77]. Activation of Cdc28 for the START transition requires its association with the positive regulatory subunits, the GI cyclius or Clns [78].…”

Section: Lessons From Yeast Cellsmentioning

confidence: 99%

Linking Protein Kinase C to Cell‐Cycle Control

Livneh

Fishman

1997

European Journal of Biochemistry

198

114

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Protein kinase C (PKC) isoenzymes are involved in diverse cellular functions, including differentiation, growth control, tumor promotion, and cell death. In recent years, evidence has began to emerge suggesting a role for PKC in cell cycle control. A paper published recently, demonstrating a functional link between PKC and cell cycle control in yeast (Marini, N. J., Meldrum, E., Buehrer, B., Hubberstey, A. V., Stone, D. E., Traynor-Kaplan, A. & Reed, S. I. (1996) EMBO J. 15, 3040-3052), strengthens this data. Thus, the existence of cell-cycle-regulated pathways involving PKC in both yeast and mammals indicate that PKC may be a conserved regulator of cell cycle events that links signal transduction pathways and the cell-cycle machinery. In this paper, we will review current data on the cell cycle components that are targets for PKC regulation.PKC enzymes appear to operate as regulators of the cell cycle at two sites, during G1 progression and G 2 M transition. In G1, the overall effect of PKC activation is inhibition of the cell cycle at mid to late G1. This cell cycle inhibition correlates with a blockage in the normal phosphorylation of the tumor suppressor retinoblastoma Rb protein, presumably through an indirect mechanism. The reduced activity of the cyclin-dependent kinase, Cdk2, appears to be the major effect of PKC activation in various cell systems. This may also underlie the inhibition of Rb phosphorylation exhibited by PKC activation. Several mechanisms were described in different studieq on the regulation of Cdk2 activity by PKC; reduced Cdk-activating kinase activity, diminished expression of the Cdk2 partners cyclins E or A, and the increased expression of the cyclin-dependent inhibitors, p2lWAF1 and p27K'P', which are capable of binding to cyclidCdk2 complexes.PKC enzymes were also shown to play a role in G2/M transition. Among the suggested mechanisms is suppression of Cdc2 activity. However, most of the published data strongly implicate PKC in lamin B phosphorylation and nuclear envelope disassembly.Keywords: protein kinase C ; cell cycle; cyclin ; cyclin-dependent kinase; Cdk inhibitor; retinoblastoma protein; p53 protein; phorbol ester; GUS transition; G2/M transition. Protein kinase C and growth regulationThe term protein kinase C (PKC) stands for a group of at least ten serinehhreonine kinases that are characterized by a high degree of similarity in their catalytic kinase domains and cysteine-rich regions [l-41. The PKC family is subdivided into three groups; the classical PKC members (a, p, y) are Ca2+ and diacylglycerol-dependent, the novel PKCs (6, E , q and d) are Ca2+-independent but diacylglycerol-dependent and the atypical PKCs ([ and 2) are not activated by Ca*+ and diacylglycerol in vitro [3, 41. This may account for the multiplicity and diversity of the cellular activities implicated to be mediated by PKC, sinceCorrespondence to

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Section: Lessons From Yeast Cellsmentioning

confidence: 99%

Linking Protein Kinase C to Cell‐Cycle Control

Livneh

Fishman

1997

European Journal of Biochemistry

198

114

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“…Yeast cell protein extracts were prepared from exponentially growing CDC28 + or cdc28 temperature-sensitive mutant (cdc28-4) cells, as described by Wittenberg and Reed (1988). The HeLa cell protein extract was kindly supplied by Clare McGowan (Scripps Clinic, La ]olla, California), as a 140,000g supernatant at a concentration of 30 rag/m1.…”

Section: Protein Kinase Assays and Sds-pa Gementioning

confidence: 99%

“…kinase has been studied extensively (Reed 1980;Mendenhall et al 1987Mendenhall et al , 1988Wittenberg and Reed 1988), and a G2 role has also been demonstrated recently {Reed and Wittenberg 1990}. In higher eukaryotes an essential role for the Cdc2/Cdc28 kinase activity has as yet only been demonstrated at the G2 to M phase of the cell cycle (Riabowol et al 1989}.…”

mentioning

confidence: 99%

“…It has been demonstrated in several systems that the active form of Cdc2/Cdc28 protein kinase exists as a multimeric complex with other proteins Draetta et al 1987Arion et al 1988;Draetta and Beach 1988;Gautier et al 1988Gautier et al , 1990Wittenberg and Reed 1988;Labbe et al 1989b;Meijer et al 1989;Pondaven et al 1990). One of the proteins that associates with Cdc2/Cdc28 has been identified as cyclin (Booher et al 1989;Labbe et al 1989b;Meijer et al 1989;Pines and Hunter 1989;Gautier et al 1990).…”

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confidence: 99%

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Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

Richardson¹,

Stueland²,

Thomas³

et al. 1990

Genes Dev.

181

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The Cksl protein is a component of the Cdc28 protein kinase in the budding yeast Saccharomyces cererisiae. This paper reports the cloning of two homologs of the S. cererisiae CKS1 gene from human cells. These homologs, CKShsl and CKShs2, both encode proteins of 79 amino acids that share considerable homology at the amino acid level with the products of CKS1 from S. cererisiae and sucl + from the fission yeast Schizosaccharomyces pombe. Both human homologs are capable of rescuing a null mutation of the S. cererisiae CKS1 gene when expressed from the S. cererisiae GALl promoter. S. pombe sucl + expressed from the GALl promoter is also capable of rescuing a S. cererisiae cksl null mutation. Ckshsl or Ckshs2 protein linked to Sepharose beads can bind the Cdc28/Cdc2 protein kinase from both S. cererisiae and human cells. The CKShsl and CKShs2 mRNAs are expressed in different patterns through the cell cycle in HeLa cells, which may reflect specialized roles for the encoded proteins.

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“…In Saccharomyces cerevisiae, cell cycle progression is mainly controlled by a single Cdk, which is encoded by the CDC28 gene (Wittenberg & Reed 1988), but Cdc28 is successively associated with different cyclin partners during the cell cycle: Cln3 during G1, Cln1/ 2 at G1/S, Clb5/6 during the S-phase, Clb3/4 and Clb1/2 at the G2 and M phases (Reed 1991;Nasmyth 1993). It would thus appear that Cln3 is the main determinant of the length of G1 by regulation of the timing of transcription of the CLN1 and CLN2 genes, while the other cyclin/ Cdc28 complexes play specific roles in cell cycle transitions, presumably by determining the substrate specificity of Cdc28.…”

Section: Introductionmentioning

confidence: 99%