ROLE OF EBNA-3A IN EBV-MEDIATED B CELL TRANSFORMATION

Project: Research project

Project Details

Description

DESCRIPTION: (Applicant's Description)

Epstein-Barr virus is one of a limited number of viruses associated with
human cancers and has a high degree of association with one of the three
largest groups of AIDS-related malignancies. The ability of EBV to
transform primary B lymphocytes is likely to play a role in the development
of these malignancies. The objective is to determine the cellular pathways
targeted by one of the six viral proteins demonstrated to be essential for
transformation, EBNA-3A, that the applicant s preliminary evidence suggests
functions as a transcription factor. Specifically, the applicant proposes
to: 1) Identify the function of EBNA-3A associated proteins. Preliminary
data demonstrates that EBNA-3A associates with at least two cellular
proteins, one of which is the J-kappa transcription factor. The unknown
EBNA-3A-associated protein(s) will be identified using the yeast two-hybrid
system. 2) Identify cellular genes regulated by EBNA-3A. The preliminary
data, as well as homology to other viral proteins, suggests that EBNA-3A is
highly likely to function as a transcriptional regulator, affecting
expression of cellular genes that contribute to EBV-mediated transformation.
EBNA-3A-regulated genes will be identified by representational difference
analysis. 3) Determine the significance of EBNA-3A function within the
context of viral infection. Lastly, the applicant will determine the
significance of those EBNA-3A functions that have already been identified,
as well as those to be identified in this application, by generating
recombinant EBV encoding EBNA-3A with mutations affecting each individual
function. By examining the ability of these recombinant EBV genomes to
immortalize primary human B lymphocytes, the applicant will determine
whether a given function contributes to EBV-mediated transformation.
Identification of EBNA-3A-associated proteins and EBNA-3A regulated genes
will enable determination of the cellular pathways targeted by EBNA-3A.
Analysis of these pathways, using EBNA-3A as a probe, is highly likely to
not only further the understanding of EBV- associated malignancies, but also
increase the knowledge of the control of cellular proliferation that may be
disrupted in other types of cancers.
StatusFinished
Effective start/end date9/30/967/31/03

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute: $235,519.00

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