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DBC2/RhoBTB2 functions as a tumor suppressor protein via Musashi-2 ubiquitination in breast cancer

Y M Choi1,2, K B Kim2, J H Lee3

  • 1KU Center for Integrated Science and Technology, Konkuk University, Seoul, South Korea.

Oncogene
|December 13, 2016
PubMed

Insights

Deleted in breast cancer 2 (DBC2) suppresses breast cancer by targeting Musashi-2 (MSI2) for degradation. This study identifies MSI2 as a key substrate, revealing a novel mechanism for DBC2

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The tumor suppressor gene DBC2 (RHOBTB2) functions as an adaptor protein in Cullin-3-based E3 ubiquitin ligases.
  • The precise substrates and mechanism of DBC2's tumor suppressor activity remain largely unknown.

Purpose of the Study:

  • To identify novel ubiquitination targets of DBC2.
  • To investigate the role of DBC2-mediated ubiquitination in breast cancer suppression.

Main Methods:

  • Genome-wide human cDNA library screening for in vitro ubiquitination targets.
  • Co-immunoprecipitation to confirm protein interactions.
  • Western blotting and proteasomal degradation assays.
  • Overexpression and knockdown studies in breast cancer cells.
  • Immunohistochemistry on breast cancer tissue microarrays.

Main Results:

  • Musashi-2 (MSI2) was identified as a novel ubiquitination target of DBC2.
  • DBC2 directly interacts with MSI2, promoting its polyubiquitination and proteasomal degradation.
  • DBC2 overexpression suppressed MSI2-associated oncogenic functions and induced apoptosis.
  • DBC2 and MSI2 protein levels were inversely correlated in breast and breast cancer tissues.

Conclusions:

  • DBC2 suppresses breast cancer tumorigenesis by targeting MSI2 for ubiquitination and degradation.
  • This study elucidates a novel molecular mechanism for DBC2 tumor suppressor function.
  • MSI2 represents a potential therapeutic target in DBC2-deficient breast cancers.

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