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Ubiquitin-Specific Protease 49 Interacts with Bax to Modulate Apoptosis

Hae-Seul Choi1, Soo-Yeon Kim2, So-Ra Kim2

  • 1Department of Bioconvergence, Graduate School, CHA University, Seongnam 13488, Republic of Korea.

International Journal of Molecular Sciences
|May 13, 2026
PubMed

Insights

Ubiquitin-specific protease 49 (USP49) deubiquitinates the apoptosis protein Bax, enhancing its mRNA levels and promoting cell death. USP49 regulates Bax via K29/K33/K63 linkages, not proteasomal degradation, acting as a stress-responsive apoptosis modulator.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Bax is a crucial protein in the Bcl-2 family, essential for initiating mitochondrial apoptosis.
  • Understanding Bax regulation is key to controlling cell death pathways in diseases like cancer.

Purpose of the Study:

  • To identify proteins interacting with Bax.
  • To elucidate the functional role of ubiquitin-specific protease 49 (USP49) in Bax regulation and apoptosis.

Main Methods:

  • Yeast two-hybrid screening to identify Bax-interacting proteins.
  • Immunoprecipitation and GST pull-down assays to confirm protein interactions.
  • Ubiquitination assays, RT-qPCR, and apoptosis assays to assess USP49 function.

Main Results:

  • USP49 directly binds to Bax.
  • USP49 reduces Bax polyubiquitination, particularly K11, K29, K33, and K63 linkages, without affecting K48-linked ubiquitination or protein stability.
  • USP49 overexpression upregulates Bax mRNA levels, enhancing apoptosis, especially under DNA damage conditions.

Conclusions:

  • USP49 regulates Bax through non-proteasomal ubiquitination (K29/K33/K63) and transcriptional upregulation.
  • USP49 acts as a stress-responsive apoptosis modulator.
  • USP49 is a potential therapeutic target for cancer treatment.
Keywords:
B-cell lymphoma 2 (Bcl-2) familydeubiquitinating enzymedeubiquitinationubiquitination

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