roughex down-regulates G2 cyclins in G1.

Thomas, Barbara J.; Zavitz, Kenton H.; Dong, Xinzhong; Lane, Mary Ellen; Weigmann, Katrin; Finley, Russell L.; Brent, Roger; Lehner, Christian F.; Zipursky, S. Lawrence

doi:10.1101/gad.11.10.1289

Cited by 73 publications

(93 citation statements)

References 48 publications

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“…Therefore, the nuclear import of Cyclin A in ofs mutants was dissociated from other aspects of the G 2 -M transition. Similar precocious nuclear import had been observed upon overexpression of Roughex (Rux), a cyclin-dependent kinase inhibitor (Avedisov et al, 2000;Gönczy et al, 1994;Thomas et al, 1997). Indeed, we found that ofs mutant spermatocytes exhibited abnormal accumulation of Rux protein, and that Rux colocalized with nuclear Cyclin A (Fig.…”

Section: Off-schedule Identifies a Distinct Pathway Controlling Spermsupporting

confidence: 56%

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

et al. 2007

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During spermatogenesis, cells coordinate differentiation with the meiotic cell cycle to generate functional gametes. We identified a novel gene, which we named off-schedule (ofs), as being essential for this coordinated control. During the meiotic G 2 phase, Drosophila ofs mutant germ cells do not reach their proper size and fail to execute meiosis or significant differentiation. The accumulation of four cell cycle regulators -Cyclin A, Boule, Twine and Roughex -is altered in these mutants, indicating that ofs reveals a novel branch of the pathway controlling meiosis and differentiation. Ofs is homologous to eukaryotic translation initiation factor eIF4G. The level of ofs expression in spermatocytes is much higher than for the known eIF4G ortholog (known as eIF-4G or eIF4G), suggesting that Ofs substitutes for this protein. Consistent with this, assays for association with mRNA cap complexes, as well as RNA-interference and phenotypic-rescue experiments, demonstrate that Ofs has eIF4G activity. Based on these studies, we speculate that spermatocytes monitor G 2 growth as one means to coordinate the initiation of meiotic division and differentiation.

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Section: Off-schedule Identifies a Distinct Pathway Controlling Spermsupporting

confidence: 56%

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

et al. 2007

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“…This phenotype is suppressed by the down-regulation of Cyclin A. Furthermore, overexpression of Rux protein induces degradation of Cyclin A and inhibits S-phase entry caused by Cyclin A accumulation (Sprenger et al, 1997;Thomas et al, 1997). Thus rux shares several features with ste9 and rum1; all proteins function as a negative regulator of G 1 progression.…”

Section: Discussionmentioning

confidence: 91%

Fission Yeast Ste9, a Homolog of Hct1/Cdh1 and Fizzy-related, Is a Novel Negative Regulator of Cell Cycle Progression during G₁-Phase

Kitamura

Maekawa

Shimoda

1998

MBoC

110

125

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When proliferating fission yeast cells are exposed to nitrogen starvation, they initiate conjugation and differentiate into ascospores. Cell cycle arrest in the G1-phase is one of the prerequisites for cell differentiation, because conjugation occurs only in the pre-Start G1-phase. The role ofste9 + in the cell cycle progression was investigated. Ste9 is a WD-repeat protein that is highly homologous to Hct1/Cdh1 and Fizzy-related. The ste9 mutants were sterile because they were defective in cell cycle arrest in the G1-phase upon starvation. Sterility was partially suppressed by the mutation in cig2 that encoded the major G1/S cyclin. Although cells lacking Ste9 function grow normally, the ste9 mutation was synthetically lethal with the wee1 mutation. In the double mutants ofste9 cdc10 ts, cells arrested in G1-phase at the restrictive temperature, but the level of mitotic cyclin (Cdc13) did not decrease. In these cells, abortive mitosis occurred from the pre-Start G1-phase. Overexpression of Ste9 decreased the Cdc13 protein level and the H1-histone kinase activity. In these cells, mitosis was inhibited and an extra round of DNA replication occurred. Ste9 regulates G1 progression possibly by controlling the amount of the mitotic cyclin in the G1-phase.

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“…The Drosophila roughex (rux) gene also controls cyclin A kinase activity in G 1 (Gö nczy et al, 1994;Thomas et al, 1994;Dong et al, 1997). Like the rum1⌬ mutant, rux mutant cells fail to arrest in G 1 , and they enter S-phase prematurely, with elevated cyclin A-associated kinase activity Sprenger et al, 1997;Thomas et al, 1997). rux may have a task similar to that of rum1 in fission yeast or SIC1 in budding yeast by preventing cyclin A from activating S-phase in early G 1 .…”

Section: Discussionmentioning

confidence: 99%

Cyclin B Proteolysis and the Cyclin-dependent Kinase Inhibitor rum1p Are Required for Pheromone-induced G₁Arrest in Fission Yeast

Stern

Nurse

1998

MBoC

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The blocking of G 1 progression by fission yeast pheromones requires inhibition of the cyclin-dependent kinase cdc2p associated with the B-cyclins cdc13p and cig2p. We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin-associated cdc2p kinase activity and for phermone-induced G 1 arrest. The cyclin-dependent kinase inhibitor rum1p is also required to maintain this G 1 arrest; it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis. We propose that rum1p acts as an adaptor targeting cdc13p for degradation by the cyclosome. In contrast, the cig2p-cdc2p kinase can be down-regulated, and the cyclin cig2p can be proteolyzed independently of rum1p. We suggest that pheromone signaling inhibits the cig2p-cdc2p kinase, bringing about a transient G 1 arrest. As a consequence, rum1p levels increase, thus inhibiting and inducing proteolysis of the cdc13p-cdc2p kinase; this is necessary to maintain G 1 arrest. We have also shown that pheromoneinduced transcription occurs only in G 1 and is independent of rum1p. INTRODUCTIONEntry into S-phase and mitosis in the eukaryotic cell cycle is controlled by the activation of cyclin-dependent kinases (CDKs). In the yeasts, both processes are initiated by a single CDK core enzyme encoded by cdc2 in fission yeast and CDC28 in budding yeast. Cdc2p and Cdc28p associate with mitotic B-type cyclins to initiate mitosis, cdc13p in fission yeast (Booher and Beach, 1988;Hagan et al., 1988;Booher et al., 1989;Moreno et al., 1989), and Clb1-4p in budding yeast (Ghiara et al., 1991;Surana et al., 1991;Fitch et al., 1992;Richardson et al., 1992) and with S-phase B-cyclins to trigger S-phase, usually cig2p in fission yeast (Fisher and Nurse, 1996;Martin-Castellanos et al., 1996;Mondesert et al., 1996) and Clb5-6p in budding yeast (Epstein and Cross, 1992;Kü hne and Linder, 1993;Schwob and Nasmyth, 1993;Schwob et al., 1994). There is considerable overlap between mitotic and S-phase B-cyclins (Schwob et al., 1994;Fisher and Nurse, 1996;Mondesert et al., 1996), and in fission yeast a single cyclin cdc13p can bring about both S-phase and mitosis (Fisher and Nurse, 1996;Mondesert et al., 1996). In budding yeast, activation of S-phase Clbp-Cdc28p protein kinase depends on the prior activation of Cdc28p associated with another class of G 1 cyclins, Cln1-3p.The mechanisms ensuring the timely inactivation and activation of cyclin B-CDK in G 1 have been studied mainly in budding yeast. S-phase Clbp-Cdc28p protein kinase is up-regulated by three independent mechanisms, all of which involve Clnp-Cdc28p kinase activity. Clnp-Cdc28p protein kinase 1) activates transcription of CLB genes (Epstein and Cross, 1992;Schwob and Nasmyth, 1993) and 2) inactivates Clbp proteolysis (Amon et al., 1994). The latter involves ubiquitin-mediated degradation of B-type cyclins, which requires the cyclosome (Sudakin et al., 1995) or anaphase-promoting complex consisting of eight subunits, including Apc1p/bimEp/cut4p (Peters et al., 1996;Yamashita et ...

show abstract

roughex down-regulates G2 cyclins in G1.

Cited by 73 publications

References 48 publications

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

Fission Yeast Ste9, a Homolog of Hct1/Cdh1 and Fizzy-related, Is a Novel Negative Regulator of Cell Cycle Progression during G₁-Phase

Cyclin B Proteolysis and the Cyclin-dependent Kinase Inhibitor rum1p Are Required for Pheromone-induced G₁Arrest in Fission Yeast

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roughex down-regulates G2 cyclins in G1.

Cited by 73 publications

References 48 publications

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation inDrosophilaspermatocytes

Fission Yeast Ste9, a Homolog of Hct1/Cdh1 and Fizzy-related, Is a Novel Negative Regulator of Cell Cycle Progression during G1-Phase

Cyclin B Proteolysis and the Cyclin-dependent Kinase Inhibitor rum1p Are Required for Pheromone-induced G1Arrest in Fission Yeast

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Fission Yeast Ste9, a Homolog of Hct1/Cdh1 and Fizzy-related, Is a Novel Negative Regulator of Cell Cycle Progression during G₁-Phase

Cyclin B Proteolysis and the Cyclin-dependent Kinase Inhibitor rum1p Are Required for Pheromone-induced G₁Arrest in Fission Yeast