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The Functional Study of Transcriptional Corepressor G-Protein Suppressor 2 (GPS2) and Tumor Suppressor Promyelocytic Leukemia (PML)

Cheng, Xiwen

Abstract Details

2010, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
We have identified G-protein pathway suppressor 2 (GPS2) as an integral component of the silencing mediator of retinoid acid and thyroid hormone receptor (SMRT) corepressor complex. Functional studies revealed that GPS2 is functionally important for estrogen receptor alpha (ERα)-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 signal transducer and activator of transcription 1 (STAT1) and downstream integrin β1 (ITGB1), thus identifying a novel pathway in which PML mediates the TNFα/IFNα 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 TNFα. We further characterized the functional ontology of these gene lists and identified groups of interesting genes that warrant future study.
Hung-Ying Kao, PhD (Advisor)
Edward Stavnezer, PhD (Committee Member)
Gary Landreth, PhD (Committee Member)
David Samols, PhD (Committee Chair)
Zhang Youwei, PhD (Committee Member)
232 p.

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Citations

  • Cheng, X. (2010). The Functional Study of Transcriptional Corepressor G-Protein Suppressor 2 (GPS2) and Tumor Suppressor Promyelocytic Leukemia (PML) [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1277741995

    APA Style (7th edition)

  • Cheng, Xiwen. The Functional Study of Transcriptional Corepressor G-Protein Suppressor 2 (GPS2) and Tumor Suppressor Promyelocytic Leukemia (PML). 2010. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1277741995.

    MLA Style (8th edition)

  • Cheng, Xiwen. "The Functional Study of Transcriptional Corepressor G-Protein Suppressor 2 (GPS2) and Tumor Suppressor Promyelocytic Leukemia (PML)." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1277741995

    Chicago Manual of Style (17th edition)