BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction.

Promyelocytic leukemia protein (PML) modulates the p53 tumor suppressor through its interaction with p53 and MDM2. We found that activated big MAP kinase 1 (BMK1) preferentially associates with PML isoform IV and disrupts PML-MDM2 interaction. Doxorubicin, a common chemotherapeutic agent, is known to promote PML-mediated p53 activation in part by ...
promoting PML-dependent MDM2 nucleolar sequestration. We discovered that BMK1 deactivation coupled with doxorubicin synergistically enhanced MDM2 nucleolar sequestration and, consequently, promoted PML-mediated p53 upregulation leading to tumor cell apoptosis in vitro and tumor regression in vivo. Collectively, these results not only suggest that BMK1 activity has a role in suppressing p53 by blocking the interaction between PML and MDM2, but also implicate that pharmacological BMK1 inhibitor should significantly enhance the anticancer capacity of doxorubicin-based chemotherapy.
Mesh Terms:
Animals, Antibiotics, Antineoplastic, Cell Line, Tumor, Doxorubicin, Enzyme Activation, HeLa Cells, Humans, Mice, Mitogen-Activated Protein Kinase 7, Neoplasm Transplantation, Nuclear Proteins, Protein Isoforms, Proto-Oncogene Proteins c-mdm2, RNA Interference, RNA, Small Interfering, Transcription Factors, Transcriptional Activation, Transplantation, Heterologous, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Oncogene
Date: Jun. 27, 2013
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