pch1 +, a Second Essential C-type Cyclin Gene in Schizosaccharomyces pombe

Furnari, Beth; Russell, Paul; Leatherwood, Janet

doi:10.1074/jbc.272.18.12100

Cited by 14 publications

(15 citation statements)

References 56 publications

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“…This high degree of similarity is also shared with an S. cerevisiae cyclin C homolog, Srb11 (32). Pch1 is an essential C-type cyclin whose function is unknown (21). SRB11 mutants were identified as suppressors of the Cs phenotype of partial truncation mutants in CTD (58), and alleles of SRB11 have been isolated in three other screens for mutations involved in the regulated repression of transcription (ssn8, are1, and ume1 mutants).…”

Section: Resultsmentioning

confidence: 99%

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Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity

Edwards

Wong

Elledge

1998

Molecular and Cellular Biology

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The gene coding for human cyclin K was isolated as a CPR (cell-cycle progression restoration) gene by virtue of its ability to impart a Far ؊ phenotype to the budding yeast Saccharomyces cerevisiae and to rescue the lethality of a deletion of the G 1 cyclin genes CLN1, CLN2, and CLN3. The cyclin K gene encodes a 357-aminoacid protein most closely related to human cyclins C and H, which have been proposed to play a role in regulating basal transcription through their association with and activation of cyclin-dependent kinases (Cdks) that phosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II). Murine and Drosophila melanogaster homologs of cyclin K have also been identified. Cyclin K mRNA is ubiquitously expressed in adult mouse and human tissues, but is most abundant in the developing germ cells of the adult testis and ovaries. Cyclin K is associated with potent CTD kinase and Cdk kinase (CAK) activity in vitro and coimmunoprecipitates with the large subunit of RNAP II. Thus, cyclin K represents a new member of the "transcription" cyclin family which may play a dual role in regulating Cdk and RNAP II activity.

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Section: Resultsmentioning

confidence: 99%

“…CTK2, a C-type cyclin, and CTKK1, a CTD kinase, form a complex in vivo, although a role in transcription has not been demonstrated (55). In addition, several related cyclin-Cdk complexes have been identified in S. pombe, but their roles in transcription or Cdk activation are unknown (4,11,21,36).…”

mentioning

confidence: 99%

Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity

Edwards

Wong

Elledge

1998

Molecular and Cellular Biology

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“…Since then, cyclins with significant homology to the cyclin box region of cyclin C have also been found in Schizosaccharomyces pombe (14,39). Except for a recent study carried out in murine cells (36), there has been no evidence supporting a critical role for C-type cyclins in cell cycle progression.…”

mentioning

confidence: 92%

The Yeast C-Type Cyclin Ctk2p Is Phosphorylated and Rapidly Degraded by the Ubiquitin-Proteasome Pathway

Hautbergue

Goguel

1999

Molecular and Cellular Biology

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The yeast CTDK-I complex has been implicated in phosphorylation of the carboxy-terminal domain of the RNA polymerase II and in transcription control. It is composed of three polypeptides: Ctk1p and Ctk2p, a cyclin-dependent kinase and a C-type cyclin subunit, respectively; and Ctk3p, a third subunit of unknown function. Cyclins are regulatory proteins whose expression is tightly controlled at the protein level. In this study, we examined the regulation of Ctk2p expression in vivo. Surprisingly, unlike what has been described for cell cycle cyclins, steady-state levels of Ctk2p are composed of two relatively abundant forms, one of them phosphorylated. We show that this phosphorylated form is extremely unstable (half-life, 5 min) and that rapid proteolysis of Ctk2p exhibits growth-related regulation. Furthermore, our data establish that similar to the case for other naturally short-lived proteins, Ctk2p degradation is mediated by the ubiquitin-proteasome pathway. This is the first demonstration that a C-type cyclin is phosphorylated and targeted to the proteasome. Strikingly, neither phosphorylation nor destruction of Ctk2p requires its associated kinase Ctk1p, a feature fundamentally different from that which has been observed for cell cycle cyclins.Cyclin-dependent protein kinases (CDKs) were first identified as central regulators of the major transitions of the eukaryotic cell division cycle. Their activity is determined by cyclin binding, by both positive and negative regulatory phosphorylation, and by polypeptide CDK inhibitors (40, 41). A single cyclin-dependent kinase subunit associates sequentially with multiple cyclin partners whose abundance fluctuates during the cell cycle (43). Indeed, one aspect of CDK regulation is triggered by the rapid destruction of their cyclin partners (23). Several studies both in yeast and in mammals have demonstrated that cyclins are selectively degraded by the ubiquitindependent proteasome pathway (9,16,53,67). Substrates are first marked for degradation by conjugation with several molecules of ubiquitin, a highly conserved 76-amino-acid-long polypeptide that is joined reversibly by a covalent linkage.

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“…pombe extracts showed that the cyclin was associated with a CTD kinase activity (23); however, the identity of the catalytic subunit was not established. Given that the Bur1/Bur2 complex is important for transcription in S. cerevisiae and that it phosphorylates the pol II CTD (18, 24), we can tentatively impute similar activities to SpCdk9/Pch1.…”

Section: Mutations Of the Kinase Active Site And T-loop Abolish Spcdkmentioning

confidence: 99%

Interactions between Fission Yeast Cdk9, Its Cyclin Partner Pch1, and mRNA Capping Enzyme Pct1 Suggest an Elongation Checkpoint for mRNA Quality Control

Pei¹,

Schwer²,

Shuman³

2003

Journal of Biological Chemistry

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RNA polymerase II (pol II) is subject to an early elongation delay induced by negative factors Spt5/Spt4 and NELF, which is overcome by the positive factor P-TEFb (Cdk9/cyclin T), a protein kinase that phosphorylates the pol II C-terminal domain (CTD) and the transcription elongation factor Spt5. Although the rationale for this arrest and restart is unclear, recent studies suggest a connection to mRNA capping, which is coupled to transcription elongation via physical and functional interactions between the cap-forming enzymes, the CTD-PO 4 , and Spt5. Here we identify a novel interaction between fission yeast RNA triphosphatase Pct1, the enzyme that initiates cap formation, and Schizosaccharomyces pombe Cdk9. The C-terminal segment of SpCdk9 comprises a Pct1-binding domain distinct from the Nterminal Cdk domain. We show that the Cdk domain interacts with S. pombe Pch1, a homolog of cyclin T, and that the purified recombinant SpCdk9/Pch1 heterodimer can phosphorylate both the pol II CTD and the C-terminal domain of S. pombe Spt5. We provide genetic evidence that SpCdk9 and Pch1 are functional orthologs of the Saccharomyces cerevisiae CTD kinase Bur1/Bur2, a putative yeast P-TEFb. Mutations of the kinase active site and the regulatory T-loop of SpCdk9 abolish its activity in vivo. Deleting the C-terminal domain of SpCdk9 causes a severe growth defect. We suggest a model whereby Spt5-induced arrest of early elongation ensures a temporal window for recruitment of the capping enzymes, which in turn attract Cdk9 to alleviate the arrest. This elongation checkpoint may avoid wasteful rounds of transcription of uncapped pre-mRNAs.The 5Ј-cap is the defining structural feature of eukaryotic mRNA. Consisting of m 7 G linked via an inverted 5Ј-5Ј triphosphate bridge to the initiating nucleoside of the transcript, the cap is formed by enzymatic modification of pre-mRNAs as they are being synthesized by RNA polymerase II (pol II). 1 Capping entails three reactions: (i) the 5Ј-triphosphate end of the nascent pre-mRNA is hydrolyzed to a diphosphate by RNA triphosphatase, (ii) the diphosphate RNA end is capped with GMP by RNA guanylyltransferase, and (iii) the GpppN cap is methylated by RNA (guanine-N7) methyltransferase (1). Targeting of cap formation to pre-mRNAs depends on interactions of the capping enzymes with the phosphorylated C-terminal domain (CTD) of the largest subunit of pol II (Ref. 2 and citations therein). Recruitment of the capping apparatus to the elongation complex requires the TFIIH-associated CTD kinase (Kin28 in yeast, Cdk7 in mammals), which phosphorylates Ser-5 of the CTD heptad repeat YSPTSPS (3, 4).Other protein-protein contacts may also be involved in coupling capping to pol II transcription elongation. The pol II elongation factor Spt5 binds directly to the triphosphatase and guanylyltransferase components of the mammalian and Schizosaccharomyces pombe capping apparatus (5, 6). The fission yeast S. pombe employs a distinctive strategy of cap targeting whereby the triphosphatase (Pct1) and guanylyltrans...

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pch1 +, a Second Essential C-type Cyclin Gene in Schizosaccharomyces pombe

Cited by 14 publications

References 56 publications

Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity

Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity

The Yeast C-Type Cyclin Ctk2p Is Phosphorylated and Rapidly Degraded by the Ubiquitin-Proteasome Pathway

Interactions between Fission Yeast Cdk9, Its Cyclin Partner Pch1, and mRNA Capping Enzyme Pct1 Suggest an Elongation Checkpoint for mRNA Quality Control

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