Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast

Bamps, Sophie; Westerling, Thomas; Pihlak, Arno; Tafforeau, Lionel; Vandenhaute, Jean; Makela, Tomi T.P.; Hermand, Damien

doi:10.1016/j.bbrc.2004.10.190

Cited by 24 publications

(23 citation statements)

References 63 publications

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“…The two proteins were later shown to form an active kinase complex (Buck et al, 1995;Damagnez et al, 1995) and to activate fission yeast CDK1-cyclin-B complexes in vitro (Lee et al, 1999). However, mutations in mcs6, mcs2 or pmh1 (which encodes the RING finger subunit) cause neither a defect in CDK activation nor cell-cycle arrest (Molz and Beach, 1993;Buck et al, 1995;Damagnez et al, 1995;Lee et al, 1999;Saiz and Fisher, 2002;Bamps et al, 2004;Lee et al, 2005).…”

Section: One Cak or Two: The Fission Yeast Variationmentioning

confidence: 99%

Secrets of a double agent: CDK7 in cell-cycle control and transcription

Fisher

2005

Journal of Cell Science

295

283

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In metazoans, cyclin-dependent kinase 7 (CDK7) has essential roles in both the cell-division cycle and transcription, as a CDK-activating kinase (CAK) and as a component of the general transcription factor TFIIH, respectively. Controversy over its double duty has been resolved, but questions remain. First, how does CDK7 achieve the dual substrate specificity necessary to perform both roles? Second, is there a deeper connection implied by the dichotomy of CDK7 function, for example similar mechanisms controlling cell division and gene expression, and/or actual coordination of the two processes? Enzymological studies have revealed solutions to the unusual substrate recognition problem, and there is evidence that the distinct functions of CDK7 can be regulated independently. Finally, despite divergence in their wiring, the CAK-CDK networks of budding yeast, fission yeast and metazoans all link transcriptional regulation with operation of the cell-cycle machinery. This connection might help to ensure that mRNAs encoding effectors of cell division are expressed at the right time in the cycle.

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Section: One Cak or Two: The Fission Yeast Variationmentioning

confidence: 99%

Secrets of a double agent: CDK7 in cell-cycle control and transcription

Fisher

2005

Journal of Cell Science

295

283

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“…There is no convincing evidence of α-tubulin aceltylation in yeast. [36][37][38] An ortholog of the mec-17 gene is not found in either the S. cerevisiae or the S. pombe genome, and the target lysine is conserved in S. cerevisiae but not in S. pombe (data not shown).…”

Section: The Case Of α-Tubulin Acetylationmentioning

confidence: 99%

A coordinated codon-dependent regulation of translation by Elongator

Bauer

Hermand²

2012

Cell Cycle

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“…While our manuscript was in review, Bamps et al (2004) also reported that disruption of pmh1 was lethal.…”

Section: A Cdk Linking Gene Expression With Cell Cycle Controlmentioning

confidence: 99%

Impairment of the TFIIH-associated CDK-activating Kinase Selectively Affects Cell Cycle-regulated Gene Expression in Fission Yeast

Lee

Miklós

et al. 2005

MBoC

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The fission yeast Mcs6 -Mcs2-Pmh1 complex, homologous to metazoan Cdk7-cyclin H-Mat1, has dual functions in cell division and transcription: as a partially redundant cyclin-dependent kinase (CDK)-activating kinase (CAK) that phosphorylates the major cell cycle CDK, Cdc2, on Thr-167; and as the RNA polymerase (Pol) II carboxyl-terminal domain (CTD) kinase associated with transcription factor (TF) IIH. We analyzed conditional mutants of mcs6 and pmh1, which activate Cdc2 normally but cannot complete cell division at restrictive temperature and arrest with decreased CTD phosphorylation. Transcriptional profiling by microarray hybridization revealed only modest effects on global gene expression: a one-third reduction in a severe mcs6 mutant after prolonged incubation at 36°C. In contrast, a small subset of transcripts (ϳ5%) decreased by more than twofold after Mcs6 complex function was compromised. The signature of repressed genes overlapped significantly with those of cell separation mutants sep10 and sep15. Sep10, a component of the Pol II Mediator complex, becomes essential in mcs6 or pmh1 mutant backgrounds. Moreover, transcripts dependent on the forkhead transcription factor Sep1, which are expressed coordinately during mitosis, were repressed in Mcs6 complex mutants, and Mcs6 also interacts genetically with Sep1. Thus, the Mcs6 complex, a direct activator of Cdc2, also influences the cell cycle transcriptional program, possibly through its TFIIH-associated kinase function. INTRODUCTIONCyclin-dependent kinases (CDKs) play a central role in driving cell division in eukaryotic organisms and also perform essential, conserved functions in the transcription cycle of RNA polymerase (Pol) II (reviewed by Morgan, 1997). Whereas most CDKs can be classified as either cell cycle or transcriptional regulators based on a preeminent physiological function, the metazoan Cdk7 complex is essential in both cell division and gene expression, as the CDK-activating kinase (CAK) and as a component of the general transcription factor IIH (TFIIH) (reviewed by Harper and Elledge, 1998). To execute its dual functions in vivo, Cdk7 has evolved distinct substrate specificities for the activation segment (T-loop) of CDKs and the carboxy-terminal domain (CTD) of the Pol II large subunit, and mechanisms to allow their independent regulation (Garrett et al., 2001;Larochelle et al., 2001). Less clear is how (or whether) the Cdk7 complex serves to coordinate cell division with gene expression.To address this question genetically, we turned to the fission yeast Schizosaccharomyces pombe, which also relies, in part, on a dual-function CDK complex to activate CDKs and phosphorylate Pol II (Buck et al., 1995;Damagnez et al., 1995;Hermand et al., 1998;Lee et al., 1999;Saiz and Fisher, 2002). The orthologue of Cdk7 in S. pombe is Mcs6, which associates with the cyclin Mcs2 and the RING-finger protein Pmh1. Both mcs6 and mcs2 were identified in genetic screens for positive regulators of Cdc2 (S. pombe Cdk1), the major cell cycle CDK (Molz et al., 1989...

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Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast

Cited by 24 publications

References 63 publications

Secrets of a double agent: CDK7 in cell-cycle control and transcription

Secrets of a double agent: CDK7 in cell-cycle control and transcription

A coordinated codon-dependent regulation of translation by Elongator

Impairment of the TFIIH-associated CDK-activating Kinase Selectively Affects Cell Cycle-regulated Gene Expression in Fission Yeast

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