The <i>sxa2</i>‐dependent inactivation of the P‐factor mating pheromone in the fission yeast <i>Schizosaccharomyces pombe</i>

Ladds, Graham; Rasmussen, Erik Michael; Young, Tom; Nielsen, Olaf; Davey, John

doi:10.1111/j.1365-2958.1996.tb02486.x

Cited by 46 publications

(60 citation statements)

References 41 publications

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“…This genetic background is required to observe P-factor-induced G 1 arrest in exponentially growing cells. Elimination of the adenylate cyclase cyr1 ϩ gene leads to constitutive expression of nutritionally controlled genes, including components of the pheromone signal transduction cascade (Maeda et al, 1990;Kawamukai et al, 1991;; sxa2 ϩ encodes a P-factor-degrading protease (Imai and Yamamoto, 1992;Ladds et al, 1996). Control…”

Section: Cdk Inhibitor Rum1p Is Required For Pheromoneinduced G 1 Arrestmentioning

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 ...

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Section: Cdk Inhibitor Rum1p Is Required For Pheromoneinduced G 1 Arrestmentioning

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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“…In addition to the map and mam genes, two other genes are known to affect mating efficiency in a mating-type-specific manner. These genes, namely, sxa1 and sxa2, have been supposed to encode putative proteases that degrade M-factor and P-factor, respectively (27), and it has been demonstrated recently that an sxa2-dependent carboxypeptidase removes the C-terminal leucine residue of P-factor (36). The sxa1 function is required for h ϩ cells and the sxa2 function is required for h Ϫ cells, although disruption of neither sxa1 nor sxa2 abolishes the mating ability completely.…”

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confidence: 99%

Schizosaccharomyces pombe map1⁺Encodes a MADS-Box-Family Protein Required for Cell-Type-Specific Gene Expression

Yabana

Yamamoto

1996

Molecular and Cellular Biology

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We cloned the Schizosaccharomyces pombe map1 gene by virtue of its ability to stimulate transcription of the sxa2 gene, which encodes a carboxypeptidase expressed specifically in h ؊ cells in response to mating-pheromone signaling. The cloned gene had a coding capacity of 398 amino acids split by two introns, and the deduced product was a protein of the MADS box family. This gene was most similar to Saccharomyces cerevisiae MCM1, which regulates cell-type-specific gene expression in budding yeast cells. Disruption of the S. pombe gene did not affect vegetative cell growth but conferred sterility. It blocked the mating ability of h ؉ cells completely and that of h ؊ cells partially. Genetic and sequencing analysis indicated that the cloned gene is map1, which was originally defined by a mutation that caused h ؉ -specific sterility. Northern (RNA) blot analysis showed that the function of map1 is absolutely essential for the expression of h ؉ -specific genes and is required for the full activation of h ؊ -specific gene expression. Overexpression of map1 resulted in enhanced transcription of cell-type-specific genes, but the range of genes affected by Map1 was restricted by the mating type of the cell. Results of yeast two-hybrid analysis suggested that Map1 may physically interact with Mat1-Pc, the product of the h ؉ -specific mating-type gene mat1-Pc. On the basis of these observations, we speculate that Map1 may be a transcriptional regulator of cell-type-specific genes similar to S. cerevisiae MCM1, whose activity is modulated by the ␣1 and ␣2 mating-type gene products.Cells of the fission yeast Schizosaccharomyces pombe initiate sexual development when starved for nutrients, especially a nitrogen source. Haploid cells of the opposite mating types, termed h ϩ (P) and h Ϫ (M), communicate by secreting mating pheromones prior to mating: h ϩ cells produce P-factor and the M-factor receptor, while h Ϫ cells produce M-factor and the P-factor receptor, in response to nutritional starvation (17, 37). This cell-type-specific production of pheromones and receptors is observed only upon nutrient deprivation. Indeed, neither diploid-nor haploid-specific gene expression during mitotic growth in S. pombe has been reported.The mating-pheromone response pathway of S. pombe provides a model system for the study of signal transduction in eukaryotic cells. This pathway involves a receptor-coupled Gprotein system (33, 49, 64) and a mitogen-activated protein (MAP) kinase cascade (18,44,46,65,67). Mutants of S. pombe that exhibit sterility in a mating-type-specific manner have been useful in the identification of factors required for pheromonal communication. Four h ϩ -specific sterility genes, named map1 through map4, and four h Ϫ -specific sterility genes, named mam1 through mam4, have been identified (11, 26, 27a, 65). The map2 gene encodes a precursor of P-factor, in which four repeats of the mature P-factor sequence are embedded (26). The gene products of map3 and mam2 are both putative seven-transmembrane proteins. Genetic e...

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“…With the exception of JY444, JY478, JY1354, JY1025, and AH109, all yeast strains were derived from JY546, which contains the sxa2ϾlacZ construct for quantification of P-factor-dependent transcription (23,24). General yeast procedures were performed as described previously (25,26) using yeast extract medium for routine cell growth and selective, defined minimal medium for all assays. Oligonucleotides were synthesized by Invitrogen.…”

Section: Methodsmentioning

confidence: 99%

A Physiologically Required G Protein-coupled Receptor (GPCR)-Regulator of G Protein Signaling (RGS) Interaction That Compartmentalizes RGS Activity

Croft

Hill²,

Bond

et al. 2013

Journal of Biological Chemistry

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Background: G protein-coupled receptors (GPCRs) interact with regulator of G protein signaling (RGS) proteins, but the mechanistic/physiological importance is unclear. Results: A GPCR-RGS interaction is mapped that localizes RGS to the plasma membrane, a requirement for physiological signaling. Conclusion:The interaction spatially regulates RGS activity to the activated GPCR. Significance: Compartmentalized RGS activity could be a novel mechanism for modulating numerous GPCR signaling pathways.

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The sxa2‐dependent inactivation of the P‐factor mating pheromone in the fission yeast Schizosaccharomyces pombe

Cited by 46 publications

References 41 publications

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

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

Schizosaccharomyces pombe map1⁺Encodes a MADS-Box-Family Protein Required for Cell-Type-Specific Gene Expression

A Physiologically Required G Protein-coupled Receptor (GPCR)-Regulator of G Protein Signaling (RGS) Interaction That Compartmentalizes RGS Activity

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The sxa2‐dependent inactivation of the P‐factor mating pheromone in the fission yeast Schizosaccharomyces pombe

Cited by 46 publications

References 41 publications

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

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

Schizosaccharomyces pombe map1+Encodes a MADS-Box-Family Protein Required for Cell-Type-Specific Gene Expression

A Physiologically Required G Protein-coupled Receptor (GPCR)-Regulator of G Protein Signaling (RGS) Interaction That Compartmentalizes RGS Activity

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Product

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

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

Schizosaccharomyces pombe map1⁺Encodes a MADS-Box-Family Protein Required for Cell-Type-Specific Gene Expression