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Fbw7 and Usp28 - enemies and allies

Lyudmyla Taranets1, Jing Zhu1, Wenshan Xu1

  • 1Comprehensive Cancer Center Mainfranken and Department of Radiation Oncology; University Hospital Würzburg ; Würzburg, Germany.

Molecular & Cellular Oncology
|June 17, 2016
PubMed

Insights

The deubiquitinase Usp28 protein prevents the degradation of oncoproteins like Myc, promoting cancer. Usp28 also inhibits Fbw7 self-ubiquitination, revealing a complex regulatory role in tumor development.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • The Fbw7 ubiquitin ligase targets oncoproteins such as Myc, Jun, and Notch for degradation.
  • Dysregulation of Fbw7 activity is implicated in various cancers.
  • Usp28 (ubiquitin-specific protease 28) is known to stabilize oncoproteins by counteracting their degradation.

Purpose of the Study:

  • To investigate the role of Usp28 in regulating Fbw7 activity.
  • To elucidate the complex interplay between Usp28 and Fbw7 in tumorigenesis.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Ubiquitination assays to analyze protein turnover.
  • Cellular models to assess tumorigenesis in the intestine.

Main Results:

  • Usp28 antagonizes Fbw7-mediated degradation of key oncoproteins (Myc, Jun, Notch).
  • Usp28 was found to counteract the autocatalytic ubiquitination of Fbw7.
  • This suggests Usp28 influences Fbw7 activity beyond just its substrates.

Conclusions:

  • Usp28 plays a multifaceted role in regulating Fbw7 activity.
  • The interaction between Usp28 and Fbw7 impacts oncoprotein stability and intestinal tumor development.
Keywords:
Fbw7SCFUsp28oncogenetumor suppressorubiquitin

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