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Bcl-2 relieves the trans-repressive function of the glucocorticoid receptor and inhibits the activation of CPP32-like

T Miyashita1, U Mami, T Inoue

  • 1Department of Genetics, National Children's Medical Research Center, Tokyo, Japan. tmiyashita@nch.go.jp

Biochemical and Biophysical Research Communications
|April 28, 1997
PubMed

Insights

Glucocorticoids trigger lymphocyte apoptosis, a process inhibited by Bcl-2. This study reveals Bcl-2 prevents glucocorticoid receptor repression of AP-1, blocking apoptosis without affecting transactivation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Glucocorticoids induce apoptosis in immature lymphocytes.
  • The anti-apoptotic protein Bcl-2 can inhibit this glucocorticoid-induced cell death.
  • Mechanisms underlying glucocorticoid-induced apoptosis and Bcl-2 inhibition remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which glucocorticoids induce apoptosis in lymphocytes.
  • To investigate how Bcl-2 inhibits glucocorticoid-induced apoptosis.
  • To determine the role of AP-1 activity and cysteine proteases in this pathway.

Main Methods:

  • Overexpression of Bcl-2 in lymphocytes.
  • Analysis of glucocorticoid receptor activity and AP-1 transcriptional activity.
  • Assays for CPP32-like and ICE-like protease activation.

Main Results:

  • Overexpressed Bcl-2 relieved glucocorticoid receptor-mediated repression of AP-1 activity.
  • Bcl-2 completely inhibited the activation of CPP32-like cysteine proteases.
  • Glucocorticoid receptor-mediated transactivation was unaffected by Bcl-2.
  • ICE-like proteases were not involved in the apoptotic pathway.

Conclusions:

  • Glucocorticoid-induced lymphocyte apoptosis may occur via repression of AP-1 transactivation, a process reversed by Bcl-2.
  • Bcl-2 inhibits apoptosis by preventing AP-1 repression and CPP32-like protease activation.
  • The findings clarify the roles of AP-1 and specific proteases in glucocorticoid-mediated apoptosis.

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