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Related Experiment Videos

A phorbol ester response element within the human T-cell receptor beta-chain enhancer.

H M Prosser1, D Wotton, A Gegonne

  • 1Imperial Cancer Research Fund, London, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|October 15, 1992
PubMed
Summary

Protein kinase C activators boost T-cell receptor beta-chain gene enhancer activity. Ets transcription factors and core-binding factor bind to the enhancer, which is negatively regulated by Ets-1 during T-cell activation.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • T-cell activation involves complex signaling pathways.
  • The T-cell receptor (TCR) beta-chain gene enhancer plays a crucial role in T-cell development and function.
  • Protein kinase C (PKC) pathway activators are known to modulate immune cell responses.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the activation of the TCR beta-chain gene enhancer by PKC pathway activators.
  • To identify specific DNA elements and transcription factors involved in regulating TCR beta-chain enhancer activity.
  • To elucidate the role of Ets transcription factors in the regulation of the TCR beta-chain enhancer.

Main Methods:

  • Analysis of mutant TCR beta-chain enhancer constructs.

Related Experiment Videos

  • Electrophoretic mobility shift assays (EMSAs) to study protein-DNA interactions.
  • Cotransfection studies to assess enhancer activity and inducibility.
  • Site-directed mutagenesis of identified regulatory elements.

    • Main Results:

    • Two key elements, beta E2 and beta E3, were identified as conferring phorbol ester inducibility to the enhancer.
    • Both beta E2 and beta E3 contain a consensus Ets-binding site and directly bind to the Ets-1 proto-oncogene product.
    • The enhancer elements also bind to core-binding factor, and mutations in the Ets-binding sites abolished inducibility.
    • Ets-1 was found to specifically repress the activity of the beta E2 element and the complete TCR beta-chain enhancer.

    Conclusions:

    • The TCR beta-chain enhancer is activated by PKC-mediated signals through a functional domain containing Ets-binding sites.
    • Ets transcription factors and core-binding factor are critical for the regulation of the TCR beta-chain enhancer.
    • Ets-1 acts as a negative regulator of the TCR beta-chain enhancer activity and inducibility.