Analysis of the Effects of BCL-2 Promoter G-Quadruplex Formation on Protein Expression

Persistent Link:
http://hdl.handle.net/10150/244406
Title:
Analysis of the Effects of BCL-2 Promoter G-Quadruplex Formation on Protein Expression
Author:
Li, Frank
Issue Date:
May-2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Bcl-2 is an anti-apoptotic protein that has been implicated in a number of human diseases, including some cancers. Within the P1 promoter region, which is involved in 80-90% of bcl-2 transcriptional control, a G-rich region (Pu39) can form various monomeric G-quadruplex folding structures, each with four of the six runs of multiple guanines present. The midG4 and 5'5G4 structures have been found to be the most stable and are the potential targets of comparative studies on transcriptional effects. Plasmids containing a luciferase reporter gene under the control of this bcl-2 P1 promoter region, along with mutants to alter or eliminate G-quadruplex formation, were constructed in order to study the ability of Pu39 to control transcription. Initial luciferase assay results in HeLa and HEK293 cells suggest that mutants designed to isolate certain G-quadruplex structures caused an overall decrease in protein expression while mutants designed to knock out major folding structures caused an increase in protein expression. DNA mutant constructs in conjunction with quadruplex-specific, quadruplex-interacting drugs appear to consistently decrease protein activity, supporting the idea that the G-quadruplex has an inhibitory effect on transcription.
Type:
text; Electronic Thesis
Degree Name:
B.S.H.S.
Degree Level:
bachelors
Degree Program:
Honors College; Physiology
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleAnalysis of the Effects of BCL-2 Promoter G-Quadruplex Formation on Protein Expressionen_US
dc.creatorLi, Franken_US
dc.contributor.authorLi, Franken_US
dc.date.issued2012-05-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractBcl-2 is an anti-apoptotic protein that has been implicated in a number of human diseases, including some cancers. Within the P1 promoter region, which is involved in 80-90% of bcl-2 transcriptional control, a G-rich region (Pu39) can form various monomeric G-quadruplex folding structures, each with four of the six runs of multiple guanines present. The midG4 and 5'5G4 structures have been found to be the most stable and are the potential targets of comparative studies on transcriptional effects. Plasmids containing a luciferase reporter gene under the control of this bcl-2 P1 promoter region, along with mutants to alter or eliminate G-quadruplex formation, were constructed in order to study the ability of Pu39 to control transcription. Initial luciferase assay results in HeLa and HEK293 cells suggest that mutants designed to isolate certain G-quadruplex structures caused an overall decrease in protein expression while mutants designed to knock out major folding structures caused an increase in protein expression. DNA mutant constructs in conjunction with quadruplex-specific, quadruplex-interacting drugs appear to consistently decrease protein activity, supporting the idea that the G-quadruplex has an inhibitory effect on transcription.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.H.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplinePhysiologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.