Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor beta (TGF-beta) plays critical roles in the control of cell proliferation, differentiation, and apoptosis. Smad proteins are substrates of the TGF-beta type I receptor and are responsible for transducing receptor signals to target genes in the nucleus. The PIAS (protein inhibitor of activated STAT) proteins were originally identified as transcriptional co-regulators of the JAK-STAT pathway. Subsequently, cross-talk between the PIAS proteins and other signaling pathways has been shown to be involved in various cellular processes. Importantly, PIAS proteins modulate TGF-beta signaling by regulating the transcriptional activity of Smad3. In this study we tested whether hZimp10, a novel PIAS-like protein, acts as other PIAS proteins to regulate Smad3-mediated transcription. We show that expression of exogenous hZimp10 enhances the transcriptional activity of Smad3, which appears to be Smad4-dependent and responsive to TGF-beta induction. Furthermore, knockdown of endogenous hZimp10 reduced the transcriptional activity of Smad3. A protein-protein interaction between Smad3 and Smad4 with hZimp10 was identified in glutathione S-transferase-pulldown and co-immunoprecipitation assays. The Miz domain of hZimp10 and the MH2 domains of Smad3 and Smad4 were mapped as the regions responsible for binding. Results from immunostaining assays further demonstrated that Smad3, Smad4, and hZimp10 co-localize within cell nuclei. Finally, we demonstrated that Smad3/4-mediated transcription is significantly impaired in response to TGF-beta induction in Zimp10 null (zimp10-/-) embryonic fibroblasts. Taken together, these results provide the first line of evidence to demonstrate a role for Zimp10 in regulating the TGF-beta/Smad signaling pathway.
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PMID:The novel PIAS-like protein hZimp10 enhances Smad transcriptional activity. 1677 50

The tumor suppressor, p53, plays critical roles in the cell cycle progression, DNA repair and apoptosis. The PIAS proteins (protein inhibitor of activated STAT) were originally identified as inhibitors of the JAK-STAT pathway. Subsequently, crosstalk between the PIAS proteins and other signaling pathways has been shown to be involved in various cellular processes. Particularly, previous studies have demonstrated that PIAS proteins regulate p53-mediated transcription through sumoylation. hZimp10, also named zmiz1, is a novel PIAS-like protein and functions as a transcriptional co-activator. We recently identified p53 to be an hZimp10 interacting protein in the yeast two-hybrid screen. The interaction between p53 and hZimp10 was confirmed by GST pull-down and co-immunoprecipitation assays. Co-localization of p53 and hZimp10 proteins was also observed within cell nuclei by immunostaining. Moreover, we show that expression of exogenous hZimp10 enhances the transcriptional activity of p53 and knockdown of endogenous hZimp10 reduces the transcriptional activity of p53. Furthermore, using chromatin immunoprecipitation assays, we demonstrate that hZimp10 binds to p53 on the p21 promoter. Finally, p53-mediated transcription is significantly impaired in Zimp10 null embryonic fibroblasts. Taken together, these results provide the first line of evidence to demonstrate a role for Zimp10 in regulating p53 function.
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PMID:The novel PIAS-like protein hZimp10 is a transcriptional co-activator of the p53 tumor suppressor. 1758 85