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Updated: Jan 17, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

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Ubiquitination-activated TAB-TAK1-IKK-NF-κB axis modulates gene expression for cell survival in the lysosomal damage

Akinori Endo1, Chikage Takahashi1, Naoko Ishibashi1

  • 1Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Elife
|September 24, 2025
PubMed

Insights

Damaged lysosomes trigger a signaling pathway involving ubiquitin chains, activating the TAB-TAK1-IKK-NF-κB axis. This promotes cell survival and communication, revealing a new role for the ubiquitin system in cellular responses.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Lysosomal damage response is crucial for cellular homeostasis.
  • Mechanisms for lysosome repair and elimination (lysophagy) are known, but early signaling pathways remain unclear.

Purpose of the Study:

  • To elucidate the early signal transduction pathways and gene expression induced by lysosomal damage.

Main Methods:

  • Transcriptome and proteome analyses were performed.
  • Investigated the role of K63-linked ubiquitin chains in lysosomal damage response.

Main Results:

  • The TAB-TAK1-IKK-NF-κB signaling axis is activated by K63-linked ubiquitin chains on damaged lysosomes.
  • This activation leads to the expression of anti-apoptotic factors and cytokines, enhancing intercellular signaling.

Conclusions:

  • Ubiquitin-regulated signaling and gene expression are critical for cell survival and communication following lysosomal damage.
  • The ubiquitin system plays a dual role in lysophagy and activating cellular signaling pathways for survival.
Keywords:
NF-κBTABTAK1cell biologyhumanlysosomal damage responseubiquitin

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