DEATH AGONIST, BID, AND DEVELOPMENT AND NEOPLASIA

Project: Research project

Description

Programmed cell death, or apoptosis, is a fundamental biological process in development and homeostasis within all multicellular organisms. Disturbances in the regulation of apoptosis may result in multiple diseases, including cancer. Understanding the process and regulation of apoptosis may provide novel clinical approaches to cancer therapy. The susceptibility to apoptosis is regulated by intracellular checkpoints of which the BCL-2 family plays a prominent role. Family members function, at least in part, through protein-protein interactions. The ratio of death agonists (BAX,BAK,BAD,BCL-Xx) and death antagonists (BCL-2, BCL-2-XL,MCL-1,A1) dictate the responses to an apoptotic signal. However, the complete pathway from proximal death signal to distal death effector mechanisms has yet to be elucidated. Toward that end, a new death agonist gene, Bid, has been cloned based on its ability to interact with both the death agonist (BAX) and death antagonist (BCL-2). BID shares with BCL-2 family members only the BH3 domain, which it requires for both protein interaction and function. BID resides in cytosol or membrane locations and may be instrumental in mediating events between cytosol and membrane compartments during apoptosis. To determine the role of BID in normal development and homeostasis, I propose: 1) to generate a Bid loss-of-function model by gene-targeting; 2) to examine BID in human tumors and determine tumor incidence in Bid-deficient mice; 3) to characterize the molecular mechanisms of BID-induced death and define the role of BH3 domain.
StatusFinished
Effective start/end date9/5/978/31/03

Funding

  • National Institutes of Health: $152,496.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $152,496.00

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Apoptosis
Neoplasms
Cytosol
Homeostasis
Biological Phenomena
Proteins
Aptitude
Membranes
Gene Targeting
Cell Death
Incidence
Genes
Therapeutics

ASJC

  • Medicine(all)