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BRD4 regulates Aurora B kinase activity.

Ballachanda N Devaiah1, Dan Cheng1, Amit K Singh1

  • 1Experimental Immunology Branch, NCI, NIH, Bethesda, MD 20892, USA.

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|September 19, 2025
PubMed
Summary
This summary is machine-generated.

Bromodomain 4 (BRD4) controls mitosis by inhibiting Aurora B kinase activity. JNK activation phosphorylates BRD4, releasing it from chromatin and enabling Aurora B to function during metaphase.

Keywords:
Aurora BBRD4 kinaseJNKMitosisMitotic kinesin

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Epigenetics

Background:

  • Bromodomain 4 (BRD4) is a key regulator of chromatin structure and transcription.
  • BRD4 plays significant roles in cancer and immune responses.
  • BRD4 remains chromatin-bound during early mitosis, unlike other transcription regulators.

Purpose of the Study:

  • To investigate the role of BRD4 in regulating mitosis.
  • To elucidate the interaction between BRD4 and Aurora B kinase.
  • To understand how BRD4's mitotic function is regulated.

Main Methods:

  • Investigated the direct interaction between BRD4 and Aurora B kinase.
  • Assessed the effect of BRD4 binding on Aurora B kinase activity.
  • Examined the phosphorylation of histone H3 and MCAK.
  • Analyzed the role of JNK activation in BRD4 release from chromatin.

Main Results:

  • BRD4 directly binds to and inhibits Aurora B kinase activity.
  • BRD4 binding prevents autophosphorylation of Aurora B and phosphorylation of histone H3 and MCAK.
  • JNK activation phosphorylates BRD4, leading to its transient release from chromatin during metaphase.
  • Aurora B activity is inversely correlated with BRD4 binding and directly correlated with JNK activation.

Conclusions:

  • BRD4 directly controls Aurora B kinase activity during mitosis.
  • JNK-mediated phosphorylation of BRD4 is a critical step for releasing it from chromatin, allowing Aurora B activation.
  • This reveals a novel regulatory mechanism for mitosis involving BRD4, Aurora B, and JNK.