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TAK1 at the crossroads of multiple regulated cell death pathways: from molecular mechanisms to human diseases

Kun Huang1,2, Qi Zhang1,3,4, Hao Wan1

  • 1Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, China.

The FEBS Journal
|March 6, 2025
PubMed

Insights

Transforming growth factor-beta-activated kinase 1 (TAK1) regulates multiple cell death pathways, impacting diseases. Targeting TAK1 offers therapeutic potential for cancer and neurological disorders.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Regulated cell death (RCD) is crucial for homeostasis and implicated in diseases.
  • Transforming growth factor-beta-activated kinase 1 (TAK1) is a key kinase in cellular signaling.
  • TAK1 links various RCD pathways, including apoptosis, necroptosis, pyroptosis, and PANoptosis.

Purpose of the Study:

  • To review TAK1's role in diverse regulated cell death pathways.
  • To summarize TAK1's downstream signaling and binding proteins.
  • To discuss therapeutic strategies targeting TAK1 for human diseases.

Main Methods:

  • Literature review of studies on TAK1 and regulated cell death.
  • Analysis of signaling pathways regulated by TAK1.
  • Synthesis of evidence on TAK1's role in disease progression.

Main Results:

  • TAK1 acts as a central regulator at the intersection of multiple RCD pathways.
  • TAK1 influences inflammatory and immune responses.
  • TAK1 dysregulation is linked to various human diseases, including cancer and neurological disorders.

Conclusions:

  • TAK1 is a critical regulator of multiple cell death forms.
  • Targeting TAK1 presents a promising therapeutic avenue for inflammatory diseases, CNS disorders, and cancers.
Keywords:
PANoptosisTAK1apoptosisnecroptosisneurological disorderregulated cell death

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