Oncogenic protein MTBP interacts with MYC to promote tumorigenesis.

Grieb BC, Gramling MW, Arrate MP, Chen X, Beauparlant SL, Haines DS, Xiao H, Eischen CM
Cancer Res. 2014 74 (13): 3591-602

PMID: 24786788 · PMCID: PMC4079748 · DOI:10.1158/0008-5472.CAN-13-2149

Despite its involvement in most human cancers, MYC continues to pose a challenge as a readily tractable therapeutic target. Here we identify the MYC transcriptional cofactors TIP48 and TIP49 and MYC as novel binding partners of Mdm2-binding protein (MTBP), a functionally undefined protein that we show is oncogenic and overexpressed in many human cancers. MTBP associated with MYC at promoters and increased MYC-mediated transcription, proliferation, neoplastic transformation, and tumor development. In breast cancer specimens, we determined overexpression of both MYC and MTBP was associated with a reduction in 10-year patient survival compared with MYC overexpression alone. MTBP was also frequently co-amplified with MYC in many human cancers. Mechanistic investigations implicated associations with TIP48/TIP49 as well as MYC in MTBP function in cellular transformation and the growth of human breast cancer cells. Taken together, our findings show MTBP functions with MYC to promote malignancy, identifying this protein as a novel general therapeutic target in human cancer.

©2014 American Association for Cancer Research.

MeSH Terms (20)

3T3 Cells Animals Apoptosis ATPases Associated with Diverse Cellular Activities Breast Neoplasms Carrier Proteins Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic DNA Helicases Female Gene Dosage HEK293 Cells Humans Mice Mice, Nude Protein Binding Proto-Oncogene Proteins c-mdm2 Proto-Oncogene Proteins c-myc Rats

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