Abstract/Details

Modulation of the human protein kinase C alpha gene promoter by AP-2 and *Sp1


2002 2002

Other formats: Order a copy

Abstract (summary)

Protein kinase C alpha (PKC alpha) is a phospholipid-dependent protein-serine/threonine kinase that plays a major role in intracellular signaling pathways associated with transformation and tumor progression. Glioblastoma multiforme (GBM) and GBM cell lines exhibit increased levels of PKC alpha compared to normal brain tissue that relates to their proliferative and invasive potential. This thesis explores the transcriptional regulation of PKC alpha and the effects of phorbol esters on PKC alpha transcription.

The activity of the PKC alpha gene promoter was assessed in U-87 GBM cells. Basal promoter activity was restricted to a region spanning −227 to +77 relative to the transcription start site. DNase I footprinting revealed multiple activator protein-2 (AP-2) binding sites and one Sp1 binding site within this region, and point mutations of two AP-2 elements resulted in a loss of DNA binding and transcriptional activation. Overexpression of Sp1 in either U-87 or insect cells increased transcription from the −227/+77 promoter region, whereas overexpression of AP-2 increased transcription only in insect cells.

Cis activation of the promoter in U-87 cells was increased by phorbol esters but not by cyclic AMP or phosphatidylinositol 3-kinase inhibitors. These results provide evidence that cis activation of the basal promoter of the human PKC alpha gene occurs through an AP-2-dependent, phorbol ester-responsive pathway, which suggests an autoregulatory manner of transcription in GBM.

Indexing (details)


Subject
Pharmacology;
Molecular biology;
Cellular biology
Classification
0419: Pharmacology
0307: Molecular biology
0379: Cellular biology
Identifier / keyword
Health and environmental sciences; Biological sciences; AP-2; Promoter; Protein kinase C; Sp1
Title
Modulation of the human protein kinase C alpha gene promoter by AP-2 and *Sp1
Author
Clark, Joannah Hackenbruck
Number of pages
107
Publication year
2002
Degree date
2002
School code
0544
Source
DAI-B 64/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780493976631, 0493976639
Advisor
Glazer, Robert I.
University/institution
Georgetown University Medical Center
University location
United States -- District of Columbia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3077285
ProQuest document ID
305459265
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305459265/abstract
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.