Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1

Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1

Bibliographic Details
Main Author: Lehmkuhl-Dakhwe, K. Virginia
Language:English
Published: Ohio University / OhioLINK 2007
Subjects:
Trip-Br1/SEI-1
Cancer Biology
Cell Signalling
Molecular Biology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1194549826
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou11945498262021-08-03T05:45:25Z Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1 Lehmkuhl-Dakhwe, K. Virginia Trip-Br1/SEI-1 Cancer Biology Cell Signalling Molecular Biology <p>Cyclins and cyclin-binding proteins interact to contribute to cell cycle regulation and aberrations in their functions/associations can contribute to inappropriate cell proliferation and cancer. Retroviral and cellular cyclins physically interact with the transcription factor Trip-Br1 as demonstrated in yeast-2-hybrid analyses. In-vitro, Trip-Br1 associates with cellular cyclins A and B and the walleye dermal sarcoma virus retroviral cyclin (WDSV rv-cyclin). These interactions are potentially important since cyclins and Trip-Br1 have been implicated in cell-cycle regulation. The WDSV rv-cyclin, rescues cyclin-deficient yeast from growth arrest and is a potent stimulator of eukaryotic cell proliferation. Trip-Br1 is implicated in the G1-S transition of the cell cycle where Trip-Br1 antagonizes the inhibitory function of p16INK4a bound to cyclin D/cdk4 allowing phosphorylation of the retinoblastoma protein (RB, p105). Trip-Br1 also functions in association with the transcription factors E2F-1 and DP-1 to transactivate the b-myb promoter in reporter assays. Given the functional characteristics of Trip-Br1 in the context of the b-myb promoter, I anticipate that Trip-Br1 may also regulate other E2F-responsive genes, implicating it in regulation of a diverse assemblage of genes involved in both pro-cell-cycle and pro-apoptotic functions. I hypothesize that the results of overexpression of Trip-Br1 on cell proliferation is dependent on the cellular context, namely the complement of intact E2F-responsive genes.</p> <p>Here, I investigate the differential regulation of pro-apoptotic genes in normal and in cells overexpressing Trip-Br1 and Trip-Br1 mutants. I show that overexpression of Trip-Br1 transactivates an artificial promoter containing 6 E2F-responsive elements and Trip-Br1 is potentially implicated in the regulation of p21 and p14 ARF promoter constructs and this regulation is dependent on an intact Trip-Br1 heptad repeat protein domain. I show that ectopic expression of Trip-Br1 increases BAX protein and mRNA levels from the BAX native locus, possibly contributing to mitochondrial-dependent cell death. Additionally, I investigate the effects of overexpression of cyclins A and B on the Trip-Br1-mediated transactivation of p53, 6xE2F, p21, ARF, and BIM promoters and investigate the significance of a putative Trip-Br1 cyclin B/cdk1 phosphorylation site on the transactivation of these promoters. Finally, I report results of comparative microarray analyses performed in cells expressing normal and ectopic Trip-Br1.</p> 2007 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1194549826 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1194549826 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Trip-Br1/SEI-1
Cancer Biology
Cell Signalling
Molecular Biology
spellingShingle Trip-Br1/SEI-1
Cancer Biology
Cell Signalling
Molecular Biology
Lehmkuhl-Dakhwe, K. Virginia
Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1
author Lehmkuhl-Dakhwe, K. Virginia
author_facet Lehmkuhl-Dakhwe, K. Virginia
author_sort Lehmkuhl-Dakhwe, K. Virginia
title Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1
title_short Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1
title_full Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1
title_fullStr Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1
title_full_unstemmed Regulation of p53, p21, ARF, BIM, and BAX by the Transcription Factor Trip-Br1
title_sort regulation of p53, p21, arf, bim, and bax by the transcription factor trip-br1
publisher Ohio University / OhioLINK
publishDate 2007
url http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1194549826
work_keys_str_mv AT lehmkuhldakhwekvirginia regulationofp53p21arfbimandbaxbythetranscriptionfactortripbr1
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