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Acetylation regulates the MKK4-JNK pathway in T cell receptor signaling

Yukihide Matsui1, Taku Kuwabara2, Toyonobu Eguchi3

  • 1Department of Molecular Immunology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan; Department of Urology, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan; Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.

Immunology Letters
|December 18, 2017
PubMed

Insights

Protein acetylation regulates T cell receptor (TCR) signaling. Cytoplasmic CREB-binding protein (CBP) addition acetylates MKK4, inhibiting the MKK4-JNK pathway and AP-1 activity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell functions rely on signaling pathways like MKK4-JNK.
  • The precise regulation of the MKK4-JNK axis in T cells is not fully understood.

Purpose of the Study:

  • To investigate the role of protein acetylation in T cell receptor (TCR) signaling.
  • To elucidate the mechanism regulating the MKK4-JNK pathway in T cells.

Main Methods:

  • Studied T cell receptor (TCR) activation in Jurkat cells.
  • Investigated the effect of cytoplasmic CREB-binding protein (CBP) overexpression.
  • Analyzed MKK4 acetylation and JNK phosphorylation.
  • Assessed transcription factor activity (AP-1, NF-κB, NFAT).

Main Results:

  • TCR activation causes nuclear-to-cytoplasmic transport of CREB-binding protein (CBP).
  • Overexpression of cytoplasmic CBP leads to MKK4 acetylation, inhibiting MKK4-JNK signaling.
  • AP-1 transcription factor activity is reduced, while NF-κB and NFAT remain unaffected.

Conclusions:

  • Protein acetylation, mediated by cytoplasmic CBP, modulates MKK4-JNK signaling following TCR activation.
  • This acetylation specifically impacts AP-1 activity, offering new insights into T cell signaling regulation.
Keywords:
AcetylationCBPMKK4Signal transductionT cells

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