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Oncogenic protein MTBP interacts with MYC to promote tumorigenesis

Brian C Grieb1, Mark W Gramling1, Maria Pia Arrate1

  • 1Authors' Affiliations: Departments of Pathology, Microbiology and Immunology and.

Cancer Research
|May 3, 2014
PubMed

Insights

Mdm2-binding protein (MTBP) is an oncogenic protein that drives cancer by interacting with MYC. Targeting MTBP alongside MYC offers a new therapeutic strategy for various human cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • MYC is implicated in numerous human cancers but remains a difficult therapeutic target.
  • The function of Mdm2-binding protein (MTBP) in cancer is largely undefined.

Purpose of the Study:

  • To investigate the role of MTBP in human cancers.
  • To identify novel binding partners and functions of MTBP.

Main Methods:

  • Co-immunoprecipitation assays to identify MTBP binding partners.
  • Analysis of MYC and MTBP expression in human breast cancer specimens.
  • Cellular transformation assays and tumor development studies in vivo.
  • Investigation of MTBP's interaction with TIP48/TIP49 and MYC.

Main Results:

  • MTBP was identified as a novel binding partner of MYC and its cofactors TIP48/TIP49.
  • MTBP is oncogenic, overexpressed in human cancers, and co-amplified with MYC.
  • MTBP enhances MYC-mediated transcription, proliferation, neoplastic transformation, and tumor growth.
  • Co-overexpression of MYC and MTBP in breast cancer correlates with reduced patient survival.

Conclusions:

  • MTBP functions with MYC to promote cancer development and malignancy.
  • MTBP represents a novel and potentially general therapeutic target for human cancers.

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