The regulation of cell division is critical for ensuring the outcome of two viable daughter cells. Improper regulation of the cell cycle can lead to aberrant proliferation and tumor formation. The human pocket proteins retinoblastoma (Rb), p107, and p130 are critical regulators of the cell cycle and contribute to tumor suppression. Their growth suppressive function is achieved through the regulation of E2F transcription factors, but within the pocket protein family, there is specificity for the particular E2F transcription factors each negatively regulates. The molecular mechanisms governing this specificity remain unknown, as does how E2F specificity contributes to the different functions observed among pocket proteins. In this study, I explore the molecular determinants governing the interactions between pocket proteins and E2Fs, how this E2F specificity may influence the function of pocket proteins, as well as the evolution of tumor suppression characteristics in the protein Rb. Using structural biology, biochemistry and biophysical techniques, we identified key regions of Rb that evolved to regulate a specific subset of E2Fs, giving rise to the unique functional activities associated with Rb.
|Commitee:||Kellogg, Doug, Stone, Michael|
|School:||University of California, Santa Cruz|
|School Location:||United States -- California|
|Source:||DAI-B 78/06(E), Dissertation Abstracts International|
|Keywords:||E2F binding specificity, Retinoblastoma pocket protein|
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