Two Regulators of Ste12p Inhibit Pheromone-Responsive Transcription by Separate Mechanisms

Olson, Karen A.; Nelson, Christopher E.; Tai, Georgia; Hung, Wesley; Yong, Carl; Astell, Caroline R.; Sadowski, Ivan

doi:10.1128/mcb.20.12.4199-4209.2000

Cited by 83 publications

(80 citation statements)

References 44 publications

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“…In contrast to Dig2, the loss of Dig1 (and/or Sfl1) caused hyper-invasiveness even in the absence of both Kss1 and Tpk2 (Table 3). This functional difference between Dig1 and Dig2 is consistent with reports that Dig1 and Dig2 interact with separate regions of Ste12 (Olson et al 2000) and that Dig1 and Dig2 incorporate differentially into transcription factor complexes (Ste12-Dig1-Dig2 and Tec1-Ste12-Dig1) (Chou et al 2006), which is consistent with distinct mechanisms of action.…”

Section: Resultssupporting

confidence: 90%

Systematic Epistasis Analysis of the Contributions of Protein Kinase A- and Mitogen-Activated Protein Kinase-Dependent Signaling to Nutrient Limitation-Evoked Responses in the Yeast Saccharomyces cerevisiae

Chen¹,

Thorner

2010

Genetics

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Cellular responses to environmental stimuli require conserved signal transduction pathways. In budding yeast (Saccharomyces cerevisiae), nutrient limitation induces morphological changes that depend on the protein kinase A (PKA) pathway and the Kss1 mitogen-activated protein kinase (MAPK) pathway. It was unclear to what extent and at what level there is synergy between these two distinct signaling modalities. We took a systematic genetic approach to clarify the relationship between these inputs. We performed comprehensive epistasis analysis of mutants lacking different combinations of all relevant pathway components. We found that these two pathways contribute additively to nutrient limitationinduced haploid invasive growth. Moreover, full derepression of either pathway rendered it individually sufficient for invasive growth and thus, normally, both are required only because neither is maximally active. Furthermore, in haploids, the MAPK pathway contributes more strongly than the PKA pathway to cell elongation and adhesion, whereas nutrient limitation-induced unipolar budding is independent of both pathways. In contrast, in diploids, upon nutrient limitation the MAPK pathway regulates cell elongation, the PKA pathway regulates unipolar budding, and both regulate cell adhesion. Thus, although there are similarities between haploids and diploids, cell type-specific differences clearly alter the balance of the signaling inputs required to elicit the various nutrient limitation-evoked cellular behaviors.

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Section: Resultssupporting

confidence: 90%

Systematic Epistasis Analysis of the Contributions of Protein Kinase A- and Mitogen-Activated Protein Kinase-Dependent Signaling to Nutrient Limitation-Evoked Responses in the Yeast Saccharomyces cerevisiae

Chen¹,

Thorner

2010

Genetics

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“…For instance, the predicted targets of the cell cycle regulator Fkh2 are enriched for the cell cycle and DNA processing functions (P ϭ 7.93 ϫ 10 Ϫ6 ). Another example is Dig1 whose set of predicted targets is enriched for genes involved in cell differentiation (P ϭ 6.47 ϫ 10 Ϫ5 ), in agreement with its functional role (30,31). Overall, for all 10 TFs having more than five predicted targets, their target sets were significantly enriched for functional categories consistent with the function(s) of the regulating TF (SI Table 6).…”

Section: Prediction Of Novel Transcriptional Interactions In Yeastmentioning

confidence: 80%

Transcriptional regulation of protein complexes within and across species

Tan

Shlomi

Feizi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Yeast two-hybrid and coimmunoprecipitation experiments have defined large-scale protein-protein interaction networks for many model species. Separately, systematic chromatin immunoprecipitation experiments have enabled the assembly of large networks of transcriptional regulatory interactions. To investigate the functional interplay between these two interaction types, we combined both within a probabilistic framework that models the cell as a network of transcription factors regulating protein complexes. This framework identified 72 putative coregulated complexes in yeast and allowed the prediction of 120 previously uncharacterized transcriptional interactions. Several predictions were tested by new microarray profiles, yielding a confirmation rate (58%) comparable with that of direct immunoprecipitation experiments. Furthermore, we extended our framework to a cross-species setting, identifying 24 coregulated complexes that were conserved between yeast and fly. Analyses of these conserved complexes revealed different conservation levels of their regulators and provided suggestive evidence that protein-protein interaction networks may evolve more slowly than transcriptional interaction networks. Our results demonstrate how multiple molecular interaction types can be integrated toward a global wiring diagram of the cell, and they provide insights into the evolutionary dynamics of protein complex regulation. data integration ͉ network alignment ͉ network evolution T his decade has seen an enormous amount of data on molecular interactions released into the public domain. Although many types of molecules comprise the cell and can interact with one another, the two types that have been measured at largest scale are protein-protein interactions (PPIs) and transcriptional interactions (TIs). The two-hybrid system (1) and coimmunoprecipitation (co-IP) followed by mass spectrometry (2) have been the two most popular technologies to obtain large-scale PPI data. For transcriptional interactions, ChIP coupled with whole-genome DNA microarray (ChIP-chip) allow one to determine the entire spectrum of in vivo DNA-binding sites for any given protein (3, 4).The availability of large-scale PPI and TI data from multiple species has made it possible to study how these two interaction types are combined toward a coordinated cellular response. Previously, PPI and TI data have been integrated to infer hybrid network motifs (5), sets of interacting genes that are differentially expressed (6) and causal pathways that explain differential gene expression (7). In other recent studies (8, 9), yeast TIs were mapped onto known protein complexes as recorded in the Munich Information Center for Protein Sequences (MIPS) database (10). Although these studies did not consider PPI data directly, they established that proteins within the same complex are often encoded by genes that are regulated by the same transcription factors (TFs). Protein complexes were further shown to exhibit expression coherency (11) and to include synergistic TF pairs (12)....

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“…During pseudohyphal growth activation of the filamentation MAP kinase pathway, Kss1 releases the inhibition of Dig1 and -2 on Ste12. A similar effect can be obtained by overproducing the Ste12 protein, or Ste12 domains that interact with the Dig1 and Dig2 proteins (44,45).…”

Section: Cph1 Cph2 and Efg1 Regulate The Same Set Of Differentiallymentioning

confidence: 85%

DNA Array Studies Demonstrate Convergent Regulation of Virulence Factors by Cph1, Cph2, and Efg1 in Candida albicans

Lane¹,

Birse²,

Zhou³

et al. 2001

Journal of Biological Chemistry

208

169

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Candida albicans, normally a human commensal, can cause fatal systemic infections under certain circumstances. Its unique ability to switch from yeast to hyphal growth in response to various environmental signals is inherent to its pathogenicity. Filamentation is regulated by multiple pathways including a Cph1-mediated mitogen-activated protein kinase pathway, an Efg1-mediated cAMP/PKA pathway, and a Cph2 pathway. To gain a general picture of how these various signaling pathways regulate differential gene expression during filamentation, we have constructed a partial C. albicans DNA array of 7,000 genes and used it to study the gene expression profiles using various mutants and growth conditions. By combining this novel technology with a new liquid medium in which cph1/cph1 is defective in filamentation, previously identified differentially expressed genes (ECE1, HWP1, HYR1, RBT1, SAPs5-6, and RBT4) are found to be regulated by all three pathways. In addition, two novel genes, DDR48 and YPL184, have been found to be differentially regulated during hyphal development and by all three pathways. This suggests that distinct filamentation signaling pathways converge to regulate a common set of differentially expressed genes. As one of the mechanisms for the observed convergence, we find that the transcription of a key regulator, TEC1, is regulated by Efg1 and Cph2. Importantly, most of the genes regulated by multiple filamentation pathways encode known virulence factors. Perhaps, C. albicans utilizes converging pathways to regulate its vital virulence factors to ensure its survival and pathogenicity in various host environments.

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Two Regulators of Ste12p Inhibit Pheromone-Responsive Transcription by Separate Mechanisms

Abstract: The yeast Saccharomyces cerevisiae transcription factor Ste12p is responsible for activating genes in response to MAP kinase cascades controlling mating and filamentous growth.

Cited by 83 publications

References 44 publications

Systematic Epistasis Analysis of the Contributions of Protein Kinase A- and Mitogen-Activated Protein Kinase-Dependent Signaling to Nutrient Limitation-Evoked Responses in the Yeast Saccharomyces cerevisiae

Systematic Epistasis Analysis of the Contributions of Protein Kinase A- and Mitogen-Activated Protein Kinase-Dependent Signaling to Nutrient Limitation-Evoked Responses in the Yeast Saccharomyces cerevisiae

Transcriptional regulation of protein complexes within and across species

DNA Array Studies Demonstrate Convergent Regulation of Virulence Factors by Cph1, Cph2, and Efg1 in Candida albicans

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