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AP4 encodes a c-MYC-inducible repressor of p21

Peter Jung1, Antje Menssen, Doris Mayr

  • 1Molecular Tumorpathology, Institute of Pathology, Ruhr University Bochum, D-44789 Bochum, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|September 27, 2008
PubMed

Insights

The oncogene c-MYC promotes cancer by upregulating AP4, which blocks cell cycle arrest and promotes proliferation. This pathway is crucial for maintaining a progenitor-like state in tumor cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • Constitutive expression of the c-MYC oncogene is common in human tumors.
  • Understanding c-MYC's downstream targets is crucial for cancer research.

Purpose of the Study:

  • To investigate the regulatory relationship between c-MYC and AP4.
  • To elucidate the role of AP4 in cell cycle control and cancer progression.

Main Methods:

  • Analysis of gene expression regulation by c-MYC and AP4.
  • Investigation of AP4's role in cell cycle arrest and apoptosis.
  • Examination of AP4 expression in different cell types and cancer.

Main Results:

  • c-MYC directly regulates AP4 expression through specific DNA motifs.
  • AP4 is essential for c-MYC-driven cell cycle reentry and repression of p21.
  • AP4 interferes with p53-mediated cell cycle arrest and sensitizes cells to DNA damage.
  • AP4 is specifically expressed in colonic progenitor and colorectal carcinoma cells.

Conclusions:

  • c-MYC utilizes AP4 to maintain cells in a proliferative, progenitor-like state.
  • AP4 acts as a key mediator in c-MYC's oncogenic function.
  • Targeting the c-MYC-AP4 pathway could offer therapeutic strategies for cancer.

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