POSTTRANSLATIONAL MODIFICATIONS OF BAD

Project: Research project

Project Details

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 date8/1/994/30/11

Funding

  • National Cancer Institute: $270,588.00
  • National Cancer Institute: $139,067.00
  • National Cancer Institute: $249,739.00
  • National Cancer Institute: $262,741.00

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