Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Abstract

The Retinoblastoma protein (pRB) is a key regulator of cell proliferation in the G1 phase of the cell cycle. The LxCxE binding cleft is a highly conserved region of pRB. Using a knock-in mouse model, called Rb1∆L, with disrupted pRB and LxCxE interactions, our lab has shown that epithelial cells from Rb1∆L/∆L mice do not respond to TGF-β1 mediated growth arrest. Using shRNAs to deplete the expression of components of LxCxE motif containing complexes, data showed that SAP18 is not involved in TGF-β1 mediated growth arrest. However, depletion of SAP30 and MTA2 compromised TGF-β1 mediated growth arrest. Furthermore, depletion of MTA2 resulted in derepression of E2F target genes in response to TGF-β while depletion of SAP30 repressed the expression of E2F target genes.

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