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Characterization of SPOC/NCoR Binding: A Thermodynamic and Structural Analysis of Corepressors in the Notch Signaling Pathway

Collins, Courtney E
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1510926401526291

Abstract Details

2017, MS, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
A highly conserved pathway that is critical in a number of cellular decisions both during development and for adult tissue homeostasis, Notch signaling is of central importance and tremendous relevance. Errors in regulation of Notch signaling can lead to a wide array of serious diseases. Consequently, understanding details of the underlying molecular mechanisms has significant clinical implications. Notch signaling operates through direct receptor-ligand interactions followed by a series of proteolytic cleavage events that release the NICD (Notch IntraCellular Domain). The NICD then translocates to the nucleus, where it binds the nuclear effector and DNA-binding protein CSL (CBF-1, Su(H), Lag-1). The transcription factor CSL can function as a transcriptional activator or repressor depending on the molecules bound to it. Therefore, characterizing the interactions of corepressors in the pathway provides valuable information about regulation of Notch signaling. In particular, the highly conserved corepressor SPEN (Split Ends), which binds additional corepressors such as NCoR (Nuclear receptor CoRepressor) through its SPOC (Spen Paralog and Ortholog C-terminal) domain, is required to fully repress Notch target genes. This project expanded on previous SPOC/phospho-NCoR studies that focused on SPOC as a novel phospho-peptide binding domain. Specifically, contributions included structural and thermodynamic analyses of the SPOC/phospho-NCoR complex, which were achieved by mutating NCoR residues known to be important for the interaction, mutating a SPOC residue shown in previous studies to potentially have a role in NCoR binding, and analyzing the effect of cyclic NCoR peptides on the interaction. Results provide further insight on the details of binding between SPOC and phospho-NCoR in repression in the Notch signaling pathway.
Rhett Kovall, Ph.D. (Committee Chair)
Andrew Herr, Ph.D. (Committee Member)
William Miller, Ph.D. (Committee Member)
54 p.
Biochemistry
Notch; SPOC; NCoR

Recommended Citations

Citations

  • Collins, C. E. (2017). Characterization of SPOC/NCoR Binding: A Thermodynamic and Structural Analysis of Corepressors in the Notch Signaling Pathway [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1510926401526291

    APA Style (7th edition)

  • Collins, Courtney. Characterization of SPOC/NCoR Binding: A Thermodynamic and Structural Analysis of Corepressors in the Notch Signaling Pathway. 2017. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1510926401526291.

    MLA Style (8th edition)

  • Collins, Courtney. "Characterization of SPOC/NCoR Binding: A Thermodynamic and Structural Analysis of Corepressors in the Notch Signaling Pathway." Master's thesis, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1510926401526291

    Chicago Manual of Style (17th edition)

ucin1510926401526291
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© 2017, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.