MDM2 binding protein (MTBP)

MDM2 binding protein (MTBP) is a multifunctional protein originally identified as a binding partner of MDM2, playing a central role in regulating the p53 tumor suppressor pathway[2][3]. MTBP modulates the E3 ubiquitin ligase activity of MDM2, stimulating p53 degradation while stabilizing MDM2 itself, hence maintaining p53/MDM2 homeostasis in unstressed cells[2]. It also participates in cell cycle checkpoint control, DNA replication initiation via interaction with Treslin/TICRR, and ensures proper chromosome segregation and spindle checkpoint activity during mitosis[3][4]. MTBP can act as a co-activator for transcription factors such as c-MYC, ZEB2, and nuclear receptor PXR, supporting cancer cell proliferation, metastasis, and drug resistance[1][4]. Its dysregulation is implicated in diverse cancers, and high MTBP expression marks poor prognosis and drug resistance, making it a potential therapeutic target and biomarker for patient selection and treatment monitoring[1][3].

Other names

Mdm2-binding proteinhMTBPMDM2BPmdm2-binding proteinMDM2 (mouse double minute 2)-binding protein104kDp53 binding protein binding protein104kDaTransformed 3T3 cell double minute 2

Modulation of MDM2-p53 axis: drugs affecting MDM2 (e.g., proteasome inhibitors) can influence MTBP-mediated p53 degradation. Drug clearance: by acting as a co-activator of PXR, MTBP regulates genes involved in drug resistance and can decrease antitumor effects of drugs like sorafenib.