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Retracted: Glucocorticoids repress bcl-X expression in lymphoid cells by recruiting STAT5B to the P4 promoter

Luciana Rocha-Viegas1, Guillermo P Vicent, José L Barañao

  • 1Departamento de Fisiología, Biología Molecular y Celular, Instituto de Fisiología, Biología Molecular y Neurociencias-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.

The Journal of Biological Chemistry
|September 9, 2006
PubMed

Insights

Glucocorticoids normally promote cell survival by increasing the anti-apoptotic bcl-X(L)/bcl-X(S) ratio. However, in T lymphocytes, they trigger apoptosis by inhibiting this ratio via STAT5B-mediated repression of the P4 promoter.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gene Regulation

Background:

  • The bcl-X gene produces isoforms with opposing roles in apoptosis, crucial for cell death regulation.
  • Glucocorticoids typically increase the anti-apoptotic bcl-X(L)/bcl-X(S) ratio in mammary cells by activating the P4 promoter.
  • Understanding cell-specific responses to glucocorticoids is vital for apoptosis research.

Purpose of the Study:

  • To investigate the effect of glucocorticoids on bcl-X expression and apoptosis in mouse thymocytes and S49 T cells.
  • To elucidate the molecular mechanisms underlying glucocorticoid-mediated regulation of the bcl-X P4 promoter in these cells.

Main Methods:

  • Analysis of gene transcription and protein recruitment to the bcl-X P4 promoter using mouse thymocytes and S49 T cells.
  • Hormonal treatment and assessment of glucocorticoid receptor (GR), STAT5B, and other co-regulators.
  • Histone modification analysis (acetylation/deacetylation) and RNA polymerase II dynamics.

Main Results:

  • Glucocorticoids inhibited P4 promoter transcription and decreased the bcl-X(L)/bcl-X(S) ratio in T lymphocytes, favoring apoptosis.
  • Hormonal treatment led to transient GR and RNA polymerase II recruitment, with sustained STAT5B binding.
  • Co-activator release, recruitment of silencing complexes (SMRT/HDAC3), histone deacetylation, and RNA polymerase II release occurred.
  • Inhibition of STAT5 reversed glucocorticoid-induced repression, restoring transcriptional activation and stable GR/RNA polymerase II recruitment.

Conclusions:

  • Glucocorticoids exert opposing effects on the bcl-X P4 promoter in different cell types, inhibiting transcription in T lymphocytes.
  • STAT5B plays a critical role in mediating glucocorticoid repression of the bcl-X P4 promoter in T cells.
  • The findings reveal a novel mechanism of gene repression involving STAT5B and chromatin remodeling in response to hormonal signals, impacting apoptosis regulation.

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