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Ubiquitination/de-ubiquitination: A promising therapeutic target for PTEN reactivation in cancer

Ke Wang1, Jun Liu2, Yun-Long Li3

  • 1State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|March 22, 2022
PubMed

Insights

Reactivating the tumor suppressor Phosphatase and tensin homolog (PTEN) is crucial for cancer treatment. Targeting PTEN ubiquitination/de-ubiquitination offers a promising strategy to restore its anticancer activity and suppress tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphatase and tensin homolog (PTEN) is a critical tumor suppressor gene frequently altered in human cancers.
  • PTEN regulates key cellular processes including proliferation, survival, and metabolism, and its reduced levels/activity promote tumor progression.
  • Current therapeutic strategies to restore PTEN activity are limited.

Purpose of the Study:

  • To review and discuss recent advancements in understanding PTEN ubiquitination and de-ubiquitination.
  • To highlight the therapeutic potential of targeting PTEN ubiquitination/de-ubiquitination for cancer treatment.
  • To provide a systematic summary to guide clinical translation.

Main Methods:

  • Literature review of recent discoveries on PTEN ubiquitination.
  • Analysis of regulatory mechanisms involving E3 ligases, de-ubiquitinases, and accessory proteins.
  • Discussion of pharmaceutical and gene-targeted inhibition strategies.

Main Results:

  • Ubiquitination/de-ubiquitination significantly impacts PTEN stability, localization, and activity.
  • New ubiquitination sites, E3 ligases, and de-ubiquitinases of PTEN have been identified.
  • Inhibition of E3 ligase-mediated PTEN ubiquitination enhances PTEN's anticancer function.

Conclusions:

  • Targeting PTEN ubiquitination/de-ubiquitination is a viable strategy for reactivating PTEN's tumor-suppressive functions.
  • A comprehensive understanding of these regulatory mechanisms is essential for developing novel cancer therapies.
  • This approach holds promise for clinical transformation in cancer treatment by restoring PTEN activity.
Keywords:
PI3K/Akt signalingPTENPTEN reactivationUbiquitinationde-ubiquitination

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