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USP11: A key regulator of cIAP2 stability and sensitivity to SMAC mimetics

Eun-Woo Lee1, Jaewhan Song1

  • 1Department of Biochemistry; College of Life Science and Biotechnology; Yonsei University ; Seoul, Korea.

Molecular & Cellular Oncology
|June 18, 2016
PubMed

Insights

Cellular inhibitor of apoptosis proteins (cIAPs) protect cancer cells. A new pathway shows cIAP2, stabilized by USP11, makes cells resistant to SMAC mimetics, impacting cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Cellular inhibitor of apoptosis proteins (cIAPs) are crucial for cancer cell survival against apoptosis.
  • Second mitochondria-derived activator of caspases (SMAC) mimetics were developed to target cIAPs.
  • Cancer cells can develop resistance to apoptosis-inducing therapies.

Purpose of the Study:

  • To investigate a novel survival pathway involving cIAP2 and USP11.
  • To understand the mechanism of resistance to SMAC mimetics.
  • To identify potential therapeutic targets for overcoming cancer cell resistance.

Main Methods:

  • Analysis of tumor necrosis factor-alpha (TNF-α) induced pathways.
  • Investigation of cIAP2 stabilization by its deubiquitylase USP11.
  • Assessment of cellular response to SMAC mimetics in the presence of the novel pathway.

Main Results:

  • Tumor necrosis factor-alpha (TNF-α) induces cIAP2 expression.
  • The deubiquitylase USP11 stabilizes cIAP2.
  • This cIAP2 stabilization confers resistance to SMAC mimetics in cancer cells.

Conclusions:

  • A novel cIAP2-USP11 survival pathway contributes to cancer cell resistance.
  • Targeting this pathway may overcome resistance to SMAC mimetics.
  • Understanding this mechanism is vital for developing effective cancer treatments.
Keywords:
DeubiquitylationSMAC mimeticsTRAILUSP11cIAP2

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