The regulation of RNA polymerase I and RNA polymerase III transcription by the pocket proteins

Sutcliffe, Josephine E (2000) The regulation of RNA polymerase I and RNA polymerase III transcription by the pocket proteins. PhD thesis, University of Glasgow.

Abstract

RB has been shown to repress pol III transcription by targeting the pol III-specific general factor TFIIIB. Work presented here demonstrates that RB binds to the BRF subunit of TFIIIB. The binding interaction between these two proteins has been shown to require the RB large pocket domain and the amino-terminal repeats of BRF. In addition, the mechanism whereby RB represses pol III transcription has been established; namely, RB does not compromise the interactions within TFIIIB, but instead disrupts the association between TFIIIB and TFIIIC and between TFIIIB and pol III. In human cancers, RB is generally inactivated by one of three means: hyperphosphorylation, mutation or viral oncoprotein sequestration. SV40-transformed cell lines displayed a diminished interaction between RB and BRF in comparison to the untransformed parental line. The association was also alleviated if RB was mutated or phosphorylated. In addition, mutant RB forms were unable to disrupt the interaction between TFIIIB and TFIIIC and between TFIIIB and pol III. RB has also been shown to repress pol I transcription. The current work demonstrated an interaction between RB and the pol I transcription factors UBF and SLl. The human and Xenopus UBF-binding domain in RB was identified as the large pocket, whilst xUBF was shown to bind RB through HMG boxes 1 and 2. The RB-related proteins p107 and p130 were investigated for their ability to undertake RB functions. Indeed, p107 and p130 were both able to interact with the pol I transcription factor UBF and the BRF subunit of the pol III transcription factor TFIIIB.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Biochemistry.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: White, Robert J.
• Date of Award: 2000
• Depositing User: Enlighten Team
• Unique ID: glathesis:2000-73265
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 26 Aug 2021 14:18
• URI: https://theses.gla.ac.uk/id/eprint/73265

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