Two Nuclear Proteins, Cin5 and Ydr259c, Confer Resistance to Cisplatin in<i>Saccharomyces cerevisiae</i>

Furuchi, Takemitsu; Ishikawa, Hirohide; Miura, Nobuhiko; Ishizuka, Miki; Kajiya, Kazuki; Kuge, Shusuke; Naganuma, Akira

doi:10.1124/mol.59.3.470

Cited by 55 publications

(49 citation statements)

References 17 publications

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“…The fact that YAP4 is responsive to such a wide plethora of environmental insults suggests an important role in the response to stress. Indeed, previous work has revealed that its overexpression is capable of relieving cellular sensitivity to a wide range of conditions and drugs, including salt (Mendizabal et al, 1998;Nevitt et al, 2004), cisplatin (Furuchi et al, 2001) and quinoline ringcontaining antimalarial drugs (Delling et al, 1998). The fact that the adduct-forming chemotherapeutic agent cisplatin acts at the level of transcriptional repression, by denying the RNA polymerase II initiation complex access to the TATA box (Vichi et al, 1997), may suggest a role for Yap4p within the realm of the basal transcriptional machinery.…”

Section: Discussionmentioning

confidence: 99%

YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae

Nevitt

Rodrigues-Pousada

2004

Yeast

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Exposure of Saccharomyces cerevisiae to several environmental insults, including conditions of oxidative, heavy metal, metalloid and heat stress, induces the expression of the YAP4 gene, previously shown to play a role in the response to hyperosmotic stress. Expression analyses in several mutant strains under pro-oxidant conditions have determined that YAP4 is regulated by the transactivators Yap1p and Msn2p. Mutation of either the Yap1p-response element (YRE), located at −517 bp from the ATG, or the most proximal stress response element (STRE) at −430 bp, is shown to strongly compromise YAP4 gene expression under these conditions. Furthermore, these two mutations in combination lead to a severe depletion of detectable mRNA levels, indicating interplay between the transcription factors Yap1p and Msn2p in the regulation of YAP4 transcription. Transcriptional activation of this gene reflects a concomitant increase in Yap4p protein levels that appear phosphorylated upon stress and negatively regulated by protein kinase A. Yap4p amino acid residues Ser89, Ser196 and Thr241 are shown to be required for protein phosphorylation and/or protein stability.

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Section: Discussionmentioning

confidence: 99%

YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae

Nevitt

Rodrigues-Pousada

2004

Yeast

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“…Additionally, only Yap 4 and 6, when over-expressed, confer CDDP resistance (18). (ii) Yap4 targets the largest number of genes and Yap1 is epistatic to the largest number of genes in both DNA damaging conditions combined.…”

Section: Discussionmentioning

confidence: 99%

“…As many as five Yaps (1, 2, 4, 5, and 6) have been implicated in the cellular response to methylmethanesulfonate (MMS), a DNA alkylating agent (12)(13)(14)(15)(16), and cis-diamminedichloroplatinum (CDDP), a DNA cross-linking agent (17,18). With regard to other stresses, Yap TFs carry out overlapping but distinct biological functions with Yap1 being the major player in oxidative stress, Yap2 in cadmium stress, Yap4 and Yap6 in osmotic stress, and Yap8 in arsenic stress (5,19).…”

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confidence: 99%

A systems approach to delineate functions of paralogous transcription factors: Role of the Yap family in the DNA damage response

Tan

Feizi

Luo

et al. 2008

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

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Duplication of genes encoding transcription factors plays an essential role in driving phenotypic variation. Because regulation can occur at multiple levels, it is often difficult to discern how each duplicated factor achieves its regulatory specificity. In these cases, a ''systems approach'' may distinguish the role of each factor by integrating complementary large-scale measurements of the regulatory network. To explore such an approach, we integrate growth phenotypes, promoter binding profiles, and gene expression patterns to model the DNA damage response network controlled by the Yeast-specific AP-1 (YAP) family of transcription factors. This analysis reveals that YAP regulatory specificity is achieved by at least three mechanisms: (i) divergence of DNAbinding sequences into two subfamilies; (ii) condition-specific combinatorial regulation by multiple Yap factors; and (iii) interactions of Yap 1, 4, and 6 with chromatin remodeling proteins. Additional microarray experiments establish that Yap 4 and 6 regulate gene expression through interactions with the histone deacetylase, Hda1. The data further highlight differences among Yap paralogs in terms of their regulatory mode of action (activation vs. repression). This study suggests how other large TF families might be disentangled in the future.ChIP-chip ͉ evolution ͉ systems biology

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“…YAP6 encodes a transcription factor homologous to YAP1p (basic leucine zipper, yeast homolog of c-Jun). Overexpression of YAP6 increases resistance to cisplatin (23), one of the most widely used drugs for cancer chemotherapy. The LA-scouting leaders are often found to scout each other.…”

Section: Longevitymentioning

confidence: 99%

Genome-wide coexpression dynamics: Theory and application

2002

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

168

223

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High-throughput expression profiling enables the global study of gene activities. Genes with positively correlated expression profiles are likely to encode functionally related proteins. However, all biological processes are interlocked, and each protein may play multiple cellular roles. Thus the coexpression of any two functionally related genes may depend on the constantly varying, yet often-unknown cellular state. To initiate a systematic study on this issue, a theory of coexpression dynamics is presented. This theory is used to rationalize a strategy of conducting a genome-wide search for the most critical cellular players that may affect the coexpression pattern of any two genes. In one example, using a yeast data set, our method reveals how the enzymes associated with the urea cycle are expressed to ensure proper mass flow of the involved metabolites. The correlation between ARG2 and CAR2 is found to change from positive to negative as the expression level of CPA2 increases. This delicate interplay in correlation signifies a remarkable control on the influx and efflux of ornithine and reflects well the intrinsic cellular demand for arginine. In addition to the urea cycle, our examples include SCH9 and CYR1 (both implicated in a recent longevity study), cytochrome c1 (mitochondrial electron transport), calmodulin (main calcium-binding protein), PFK1 and PFK2 (glycolysis), and two genes, ECM1 and YNL101W, the functions of which are newly revealed. The complexity in computation is eased by a new result from mathematical statistics.gene expression ͉ microarray ͉ urea cycle ͉ correlation ͉ glycolysis M icroarrays have generated an enormous amount of geneexpression data from a variety of biological studies (1-5). After proper preprocessing, the data can be stored as a matrix of real numbers with N rows and m columns. Rows represent the gene-expression profiles, and columns represent the cell types, time points, or environmental or other experimental conditions under which the mRNA samples are taken. To elucidate microarray data, most methods (6-10) rely on the notion of profile similarity as described for Fig. 1. It is argued that coexpressed genes are likely to encode proteins that participate in a common structural complex, metabolic pathway, or biological process (6, 10).Despite the many successful applications reported in the literature, there is an important issue that is hard to address by profile-similarity analysis. As is known, all biological processes are interlocked, and many proteins have multiple cellular roles. Two proteins engaged in a common process under certain conditions may disengage and embark on activities of their own under other conditions, which implies that both the strength and pattern of association between two gene profiles may vary as the intrinsic cellular-state changes. Weaver (11) discussed two transcription factors, Max and thyroid hormone receptor (TR). They can serve either as activators or repressors depending on other molecules bound to them. Max can bind to Myc and form a M...

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Two Nuclear Proteins, Cin5 and Ydr259c, Confer Resistance to Cisplatin inSaccharomyces cerevisiae

Cited by 55 publications

References 17 publications

YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae

YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae

A systems approach to delineate functions of paralogous transcription factors: Role of the Yap family in the DNA damage response

Genome-wide coexpression dynamics: Theory and application

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