REGULATION OF APOPTOSIS BY VIRAL TRANSFORMING PROTEINS

Project Details

Description

Adenovirus encodes two genes involved in transformation, E1A and E1B,
which cooperate to transform primary rodent cells.The E1A gene products
stimulate cell proliferation but fail to transform cells alone due to the
induction of programmed cell death (apoptosis). Expression of the E1B
gene or the human bcl-2 proto-oncogene, blocks E1A-induced cell death to
produce transformation with high efficiency. The E1B gene encodes two
products the l9K and 55K proteins that are unique proteins. Both of these
proteins enhance transformation by E1A by blocking induced cell death.
Additionally, the E1B 19K protein can block apoptosis induced by tumor
necrosis factor-a (TNF-a) and anti-Fas antibodies. Recent results from
Dr. White's laboratory has shown that the E1A proteins induce p53 which in
turn induces apoptosis. The E1B 55K protein directly binds p53 and
presumably interferes with it's function like SV40 T antigen. The
mechanism of action of the E1B l9K protein in suppression of p53 is
unknown. The aim of this proposal is to ascertain the mechanism by which
apoptosis by p53 is regulated. The approach is to define how E1A, c-myc,
TNF-a, and anti-Fas antibodies induce p53 and apoptosis and how the E1B
l9K and bcl-2 proteins block this effect.
StatusFinished
Effective start/end date3/1/941/31/04

Funding

  • National Institutes of Health: $193,821.00
  • National Institutes of Health: $200,230.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $210,194.00
  • National Institutes of Health
  • National Institutes of Health: $161,886.00
  • National Institutes of Health

ASJC

  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.