| We have identified G&barbelow-protein p&barbelowathway s&barbelowuppressor 2&barbelow (GPS2) as an integral component of the s&barbelowilencing m&barbelow&barbelowediator of r&barbelowetinoid acid and t&barbelowhyroid hormone receptor (SMRT) corepressor complex. Functional studies revealed that GPS2 is functionally important for estrogen receptor alpha (ERalpha)-mediated transcriptional regulation, and that GPS2/SMRT complex is important for maintaining normal proliferation of MCF-7 breast cancer cells. The promyelocytic leukemia protein (PML) is a well-known tumor suppressor, but its role in endothelial cells (ECs) is largely unknown, despite its high expression in endothelium and inflamed tissues. We have demonstrated that PML negatively regulates angiogenesis and cell migration, reconciling with upstream s&barbelowignal t¯ransducer and a&barbelowctivator of t&barbelowranscription 1&barbelow (STAT1) and downstream i&barbelownt&barbeloweg&barbelowrin beta1 (ITGB1), thus identifying a novel pathway in which PML mediates the TNFalpha/IFNalpha signaling in ECs. Finally, we carried out microarray analysis in ECs and identified the differentially expressed genes when PML is knocked down and/or when cells are treated with TNFalpha. We further characterized the functional ontology of these gene lists and identified groups of interesting genes that warrant future study. |
