Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Saccharomyces cerevisiae YAP2 gene encoding an AP-1-like transcriptional activator protein was cloned by selection for genes that confer pleiotropic drug resistance when present in high copy number. The novel YAP2 gene encodes a protein of 45827 daltons and is homologous in part to a known transcriptional activator protein encoded by YAP1/PDR4/SNQ3/PAR1. Homology was found only in both terminal regions. The N-terminal portion contains a region rich in basic amino acids, followed by a "leucine zipper" motif. Overexpression of YAP2 led to the induction of expression of an AP-1 recognition element (ARE)-dependent promoter. The yap1 disruptant has been shown to be sensitive to H2O2. In this study, we demonstrated that the yap1 disruptant is also unable to grow in medium containing 150 microM cadmium, whereas the yap2 disruptant exhibited no significant phenotypes. However, YAP2 in high copy number did suppress cadmium sensitivity, but not H2O2 sensitivity of the yap1 disruptant. YAP1 was able to mediate both cadmium- and H2O2-induced transcriptional activation of an ARE-dependent promoter. A high-copy-number plasmid bearing YAP2 mediated cadmium-induced transcriptional activation of this promoter. The inductions were prevented by the antioxidant N-acetyl-L-cysteine.
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PMID:Stress-induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the Jun family of transcriptional activators in Saccharomyces cerevisiae. 810 71

The ErbB-4 receptor protein-tyrosine kinase is proteolytically processed by membrane proteases in response to the ligand or 12-O-tetradecanoylphorbol-13-acetate stimulation resulting in the cytoplasmic fragment translocating to the cell nucleus. The WW domain-containing co-transcriptional activator Yes-associated protein (YAP) associates physically with the full-length ErbB-4 receptor and functionally with the ErbB-4 cytoplasmic fragment in the nucleus. The YAP.ErbB4 complex is mediated by the first WW domain of YAP and the most carboxyl-terminal PPXY motif of ErbB-4. In human tissues, we documented the expression of YAP1 with a single WW domain and YAP2 with two WW domains. It is known that the COOH-terminal fragment of ErbB4 does not have transcriptional activity by itself; however, we show here that in the presence of YAP its transcriptional activity is revealed. There is a difference in the extent of transactivation activity among YAP isoforms: YAP2 is the stronger activator compared with YAP1. This transactivation is abolished by mutations that abrogate the YAP.ErbB4 complex formation. The unphosphorylatable mutation that increases the nuclear localization of YAP increases transcription activity. The COOH-terminal fragment of ErbB-4 and full-length YAP2 overexpressed in cells partially co-localize to the nucleus. Our data indicate that YAP is a potential signaling partner of the full-length ErbB4 receptor at the membrane and of the COOH-terminal fragment of ErbB-4 that translocates to the nucleus to regulate transcription.
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PMID:WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. 1280 3