βTrCP1 promotes SLC35F2 protein ubiquitination and inhibits cancer progression in HeLa cells

Jencia Carminha Colaco1, Arun Pandian Chandrasekaran1, Janardhan Keshav Karapurkar1

  • 1Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, South Korea.

Insights

Beta-transducin repeat-containing protein 1 (βTrCP1) targets solute carrier family 35 F2 (SLC35F2) for degradation, acting as a tumor suppressor. Depleting βTrCP1 enhances SLC35F2 levels and promotes cancer progression.

Area of Science:

  • Molecular biology
  • Cancer research
  • Biochemistry

Background:

  • Solute carrier family 35 F2 (SLC35F2) is implicated in cancer progression.
  • Understanding SLC35F2 regulation is crucial for cancer therapy.

Purpose of the Study:

  • To identify the E3 ligase responsible for SLC35F2 protein degradation.
  • To investigate the role of βTrCP1 in regulating SLC35F2 levels and cancer cell behavior.

Main Methods:

  • Co-immunoprecipitation to identify interacting proteins.
  • Western blotting to assess protein levels and half-life.
  • Cellular assays to evaluate cell growth, migration, invasion, and colony formation.

Main Results:

  • Beta-transducin repeat-containing protein 1 (βTrCP1) directly interacts with and ubiquitinates SLC35F2, reducing its protein half-life.
  • A negative correlation was observed between βTrCP1 and SLC35F2 mRNA expression in cancer cell lines.
  • βTrCP1 depletion led to SLC35F2 accumulation and enhanced cancer cell phenotypes (growth, migration, invasion, colony formation).

Conclusions:

  • βTrCP1 functions as a tumor suppressor by degrading SLC35F2.
  • βTrCP1 depletion promotes SLC35F2-mediated carcinogenesis.
  • βTrCP1 represents a potential therapeutic target for cancers involving SLC35F2.

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