The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase

V Subramaniam1, H Li, M Wong

  • 1Laboratory of Molecular Pathology and Molecular and Cellular Biology Research, Sunnybrook and Women's College Health Sciences Centre, CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Ontario, Canada.

British Journal of Cancer
|October 17, 2003
PubMed

Insights

RNF11 protein is overexpressed in invasive breast cancer and interacts with Smurf2. This interaction restores transforming growth factor-beta (TGF-beta) signaling responsiveness, suggesting a role for RNF11 in cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The T2A10 clone, now known as RNF11, was identified from a tumor messenger RNA library.
  • RNF11 contains a RING-H2 domain and a PY motif, crucial for protein-protein interactions.

Purpose of the Study:

  • To investigate the role of RNF11 protein in various tumor types.
  • To elucidate the interaction mechanism between RNF11 and Smurf2.
  • To determine the functional consequence of RNF11-Smurf2 interaction on TGF-beta signaling.

Main Methods:

  • Tissue microarray analysis using polyclonal antibodies to detect RNF11 protein expression.
  • GST pulldown and immunoprecipitation assays to study protein interactions.
  • Transfection assays to assess TGF-beta signaling responsiveness.

Main Results:

  • RNF11 protein is overexpressed in invasive breast cancer and weakly expressed in kidney and prostate tumors.
  • RNF11 interacts with Smurf2 via its PY motif, leading to mutual ubiquitination.
  • Overexpression of RNF11 restores TGF-beta signaling responsiveness in transfected cells.

Conclusions:

  • RNF11 is implicated in breast cancer pathogenesis due to its overexpression.
  • The interaction between RNF11 and Smurf2 modulates TGF-beta signaling.
  • RNF11 may serve as a potential therapeutic target for restoring TGF-beta pathway activity in cancer.

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