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Updated: May 21, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

TRC8 suppresses tumorigenesis through targeting heme oxygenase-1 for ubiquitination and degradation

P-H Lin1, W-M Lan, L-Y Chau

  • 1Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

Oncogene
|June 13, 2012
PubMed

Insights

The TRC8 gene degrades the HO-1 enzyme, suppressing kidney cancer growth. TRC8-mediated HO-1 degradation is crucial for controlling cancer progression and tumor suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The TRC8 gene, encoding an endoplasmic reticulum-resident E3 ligase, is implicated in hereditary kidney cancer.
  • TRC8 demonstrates tumor-suppressive effects via its E3-ligase activity.
  • Identifying TRC8's substrates is key to understanding its tumor suppression mechanisms.

Purpose of the Study:

  • To identify physiological substrates of TRC8.
  • To elucidate the molecular mechanisms of TRC8-mediated tumor suppression.
  • To investigate the role of TRC8 and its substrate HO-1 in cancer.

Main Methods:

  • Investigated TRC8's interaction with heme oxygenase-1 (HO-1).
  • Assessed the effects of TRC8 expression and HO-1 depletion on cancer cell growth, migration, and invasion.
  • Analyzed HO-1 downregulation-induced effects on cell cycle, reactive oxygen species, and DNA damage checkpoints.

Main Results:

  • TRC8 targets heme oxygenase-1 (HO-1) for ubiquitination and degradation.
  • Ectopic TRC8 expression inhibits HO-1-driven cancer cell proliferation and metastasis.
  • HO-1 depletion counteracts the pro-tumorigenic effects of TRC8 knockdown.
  • HO-1 downregulation in renal carcinoma cells causes G2/M mitotic delay via increased ROS and DNA damage checkpoint activation.

Conclusions:

  • HO-1 plays a tumorigenic role in cancer.
  • TRC8-mediated degradation of HO-1 is essential for tumor suppression.
  • This pathway is critical for controlling cancer cell growth, migration, and invasion.

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