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Identification of REPS2 as a putative modulator of NF-kappaB activity in prostate cancer cells

Fred Penninkhof1, J Anton Grootegoed, Leen J Blok

  • 1Department of Reproduction and Development, Erasmus MC, Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.

Oncogene
|June 9, 2004
PubMed

Insights

Researchers found that the protein REPS2 interacts with NF-kappaB subunit p65. Decreased REPS2 in prostate cancer may lead to increased NF-kappaB activity, promoting resistance to apoptosis during disease progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • REPS2 protein is involved in endocytosis and signaling pathways.
  • REPS2 expression decreases in androgen-independent prostate cancer.
  • NF-kappaB signaling is upregulated during prostate cancer progression.

Purpose of the Study:

  • To identify REPS2 interacting partners.
  • To investigate the functional consequences of REPS2 downregulation in prostate cancer.

Main Methods:

  • Yeast and mammalian two-hybrid assays.
  • Analysis of crystal structure data.
  • Cell culture and stimulation with phorbol ester (PMA).

Main Results:

  • NF-kappaB subunit p65 identified as a REPS2 interacting partner.
  • The NPF-motif in p65 binds to the EH domain of REPS2.
  • REPS2-p65 interaction is sensitive to PMA stimulation.
  • REPS2 downregulation correlates with increased NF-kappaB activity in advanced prostate cancer.

Conclusions:

  • Loss of REPS2-p65 interaction may contribute to increased NF-kappaB activity.
  • Decreased REPS2 expression could drive resistance to apoptosis in prostate cancer cells.
  • REPS2 downregulation is a potential mechanism for androgen-independent growth and therapeutic resistance.

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