Accession Number:

AD1039525

Title:

Novel molecular targets for kRAS downregulation: promoter G-quadruplexes

Descriptive Note:

Technical Report,15 Aug 2014,14 Aug 2016

Corporate Author:

University of Mississippi University United States

Personal Author(s):

Report Date:

2016-11-01

Pagination or Media Count:

27.0

Abstract:

The aim of this project was to characterize the biologically relevant non-canonical G-quadruplex G4 structure within the promoter of the kRAS oncogene, and to determine the transcriptional regulation of the kRAS gene, particularly as it relates to the G4-forming regions. Throughout the proposal, we elucidated a predominant G4 structure within the mid-G4-forming region of the promoter under varying co-solvent and nucleoplasm conditions, and described the structure as having mixed parallelanti-parallel loops of lengths 2810 in the 5-3 direction. Using selective small molecules for the mid- and near-G4 regions, we further supported the ideal target for therapeutic development to be the mid-region structure. In support of aim 2, we examined the binding and functional effects of transcription factors predicted to bind to the G4-forming regions Sp1, MAZ, and p53. While some of these silenced transcription, we expanded our search for activators to the entire promoter, examined the effects of E2F, AP1 and PPAR-gamma and searched for more interactive agents by LC-MSMS.

Subject Categories:

  • Biochemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE