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Proto-oncogenic properties of the DP family of proteins

K Jooss1, E W Lam, A Bybee

  • 1Laboratory of Eukaryotic Molecular Genetics, MRC National Institute of Medical Research, Mill Hill, London.

Oncogene
|April 20, 1995
PubMed

Insights

The DP (dimerization partner) proteins, DP-1 and DP-2, possess proto-oncogenic activity and can cooperate with Ras signaling to transform cells. Their oncogenic function may operate independently of E2F-mediated transcription.

Area of Science:

  • Cellular and Molecular Biology
  • Oncogenesis
  • Signal Transduction

Background:

  • The DRTF1/E2F transcription factor complex regulates cellular proliferation through interactions with cell cycle regulators.
  • DRTF1/E2F activity depends on heterodimerization of DP and E2F proteins, with DP-1 activity influenced by cell cycle control.

Purpose of the Study:

  • To investigate the role of DP proteins (DP-1 and DP-2) in cellular growth regulation and oncogenesis.
  • To determine if DP proteins integrate with growth-regulating pathways, such as Ras signaling.
  • To elucidate the mechanism of DP-mediated oncogenic activity.

Main Methods:

  • Co-operation assays using activated Ha-ras and DP proteins (DP-1, DP-2) in rat embryo fibroblast transformation.
  • Analysis of dominant-negative and mutant DP-1 proteins to assess their oncogenic activity and target pathways.

Main Results:

  • DP-1 and DP-2 proteins integrate with the Ras signal transduction pathway.
  • Activated Ha-ras co-operates with DP-1 or DP-2 to transform rat embryo fibroblasts, demonstrating proto-oncogenic activity.
  • DP-1's oncogenic activity appears to be mediated through an E2F-independent mechanism.

Conclusions:

  • DP genes (DP-1 and DP-2) function as proto-oncogenes.
  • Aberrant regulation of DP protein activity contributes to uncontrolled cellular proliferation.
  • DP proteins possess an E2F-independent effector function in mediating oncogenesis.

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