Disease relevance of CIN5

• Our results suggest that Cin5 and Ydr259c might be involved in pleiotropic drug-resistance and might protect yeast against the toxicity of cisplatin and other alkylating agents via a single mechanism [1].
• 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 [2].

High impact information on CIN5

• In addition, unlike other yap mutations tested, yap4 (cin5) mutations affect chromosome stability, and they suppress the cold-sensitive phenotype of yap1 mutant strains [3].
• We isolated two genes, CIN5 and YDR259c, that increased resistance to cisplatin when overexpressed in Saccharomyces cerevisiae [1].
• These genes encoded two proteins, Cin5 and Ydr259c, that were homologous to yAP-1, a basic leucine zipper transcriptional factor that is known to mediate cellular resistance to various toxic agents [1].
• Cross-resistance assays determined that STI1 also conferred resistance to mefloquine (3.4-fold), while CIN5 also conferred resistance to mefloquine (9.6-fold) and chloroquine (5.4-fold) [4].
• Overexpression of the yeast genes CIN5 (a member of the family of bZIP transcription factors), STII (a Hsp90 cochaperone), and YOR273c (a member of the major facilitator superfamily of transmembrane transporters) conferred 3.9-, 7.0-, and 4.3-fold resistance to quinidine, respectively, over that of control yeast [4].

Biological context of CIN5

• YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae [2].
• 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 [2].
• This result was further substantiated by the fact that full YAP4 induction requires the two more proximal stress response elements [5].

Associations of CIN5 with chemical compounds

• Deletion of CIN5 led to increased chitosan sensitivity [6].

Regulatory relationships of CIN5

• Expression analyses in several mutant strains under pro-oxidant conditions have determined that YAP4 is regulated by the transactivators Yap1p and Msn2p [2].

Other interactions of CIN5

• The second was a Crz1p-mediated response, which is delayed compared to the Cin5p response [6].
• Induction, under the conditions tested so far, requires the presence of the transcription factor Msn2p, but not of Msn4p, as YAP4 mRNA levels are depleted by at least 75% in the msn2 mutant [5].

References