Interaction of the DNA -Bound Estrogen Receptor With Coregulatory Proteins
Likhite, Varsha Sharad
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/84799
Description
Title
Interaction of the DNA -Bound Estrogen Receptor With Coregulatory Proteins
Author(s)
Likhite, Varsha Sharad
Issue Date
2003
Doctoral Committee Chair(s)
Nardulli, Ann M.
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Biochemistry
Language
eng
Abstract
Estrogen receptors (ERs) alpha and beta are members of a large family of transcription factors that regulate gene expression in response to estrogen. Although the role of ligand in altering coactivator recruitment and transcription has been well documented, the effect of DNA-binding on coregulator recruitment has not been addressed. On binding to the estrogen response elements (EREs) in the target genes the ERs undergo DNA-induced changes in conformation. This study investigates the role of DNA-induced receptor conformations on coregulator recruitment. Here we have documented an ERE-dependent recruitment of coactivator proteins, amplified in breast cancer (AIB1) and transcription intermediary factor (TIF2) to ERalpha and ERbeta. In our efforts to identify novel interactions with the DNA-bound receptor, we have isolated several proteins that interact with the A2 ERE-bound ERalpha using DNA pull-down and agarose gel shift assays. Identification of the components of these complexes reveal proteins involved in several cell processes including, transcription, DNA repair and replication, G-protein modulation, and scavengers of superoxide radicals. Investigation of the association of ERalpha with the DNA repair protein, 3-methyadenine DNA glycosylase (MPG) reveals that this interaction modulates estrogen responsiveness and alters DNA repair. Taken together, these studies demonstrate multiple roles ER plays at the promoter. The DNA-bound receptor is involved in differential recruitment of coactivator proteins and is associated with proteins involved in other processes integrating various cell signals to modulate ER-mediated transcription.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
