POSTTRANSLATIONAL MODIFICATIONS OF BAD

Project: Research project

Description

DESCRIPTION: (adapted verbatim from the investigator's abstract) Overexpression of Bcl-2 contributes not only to the origins of cancer but also to difficulties in treating it, because Bcl-2 can block or markedly impair the induction of apoptosis by essentially all chemotherapeutic drugs and radiation. Tumor cells can also become resistant to therapy by reducing their expression of pro-apoptosis proteins such as Bax, as opposed to increasing their levels of Bcl-2. The precise biochemical mechanisms by which Bcl-2 family proteins exert their influence on cell life and death however remain far from clear. The investigator and other researchers have shown that the kinases Raf- and Akt can phosphorylate BAD, a pro-apoptotic member of Bcl-2 family, and abrogate its apoptosis-inducing effects in cells. In addition, their preliminary investigations demonstrated that the Ca2+-activated protein phosphatase calcineurin induces dephosphorylation of BAD, promoting its association with anti-apoptotic Bcl-2 family proteins and nullifying their cell survival activity. These findings suggest that the activity of BAD can be modulated by specific signal transduction molecules and suggest a need of better understanding the mechanisms that regulate the post-translational modifications of this cell death promoter. The goals of this proposal are to define the mechanisms that account for the post-translational modifications of BAD and to explore the physiological significance of this potentially important signaling pathway for controlling cell death in human cancer cells. The role of calcineurin-mediated dephosphorylation of BAD with regards to tumor cell responses to chemotherapeutic drugs and radiation will also be determined. The results obtained might provide insights as to how to render human cancer cells more sensitive to chemotherapeutic drugs and radiotherapy.
StatusFinished
Effective start/end date8/1/993/31/17

Funding

  • National Institutes of Health: $145,882.00
  • National Institutes of Health: $175,963.00
  • National Institutes of Health: $249,040.00
  • National Institutes of Health: $241,569.00
  • National Institutes of Health: $249,040.00
  • National Institutes of Health: $249,040.00
  • National Institutes of Health: $262,741.00
  • National Institutes of Health: $270,588.00
  • National Institutes of Health: $249,739.00
  • National Institutes of Health: $186,679.00
  • National Institutes of Health: $170,839.00
  • National Institutes of Health: $128,510.00
  • National Institutes of Health: $181,241.00
  • National Institutes of Health: $277,100.00
  • National Institutes of Health: $234,098.00
  • National Institutes of Health: $139,067.00

Fingerprint

Mitochondrial Membranes
Apoptosis
Post Translational Protein Processing
Neoplasms
bcl-2-Associated X Protein
Cell Death
Morphogenesis
Phosphorylation
Membranes
Radiation
Calcineurin
Proteins
Research Personnel
Pharmaceutical Preparations
Intracellular Membranes
Interleukin-3
BH3 Interacting Domain Death Agonist Protein
Homozygote
Ataxia
Caspases