Tumor suppressor BLU enhances pro-apoptotic activity of sMEK1 through physical interaction
pmid: 22349239
Tumor suppressor BLU enhances pro-apoptotic activity of sMEK1 through physical interaction
BLU is a tumor suppressor that acts as a transcriptional regulator through the association with cellular components. However, the working mechanism of BLU in cellular functions was not understood. We found that BLU directly interacts with sMEK1, a regulatory subunit of protein phosphatase 4. Furthermore, we determined the binding domains that are required for interaction between BLU and sMEK1. The N-terminal of BLU was observed to interact with the C-terminal of sMEK1. Binding activity was confirmed by the BLU-dependent increase of sMEK1 expression, as well as by the induced apoptotic activity. Also, expression of BLU and sMEK1 was down-regulated in ovarian and cervical patients, and was hypermethylated. These findings indicate that BLU can mediate the pro-apoptotic activity through the induction of sMEK1.
- Johns Hopkins University School of Medicine United States
- Yong In University Korea (Republic of)
- Johns Hopkins Medicine United States
- Breast Cancer Over Time United States
- National Cancer Center Korea (Republic of)
Ovarian Neoplasms, Tumor Suppressor Proteins, Cell Cycle, Molecular Sequence Data, Uterine Cervical Neoplasms, Apoptosis, Gene Expression Regulation, Neoplastic, Cytoskeletal Proteins, HEK293 Cells, Proto-Oncogene Proteins c-bcl-2, Cell Line, Tumor, Protein Interaction Mapping, Phosphoprotein Phosphatases, Humans, Female, Amino Acid Sequence, RNA, Messenger, Cells, Cultured
Ovarian Neoplasms, Tumor Suppressor Proteins, Cell Cycle, Molecular Sequence Data, Uterine Cervical Neoplasms, Apoptosis, Gene Expression Regulation, Neoplastic, Cytoskeletal Proteins, HEK293 Cells, Proto-Oncogene Proteins c-bcl-2, Cell Line, Tumor, Protein Interaction Mapping, Phosphoprotein Phosphatases, Humans, Female, Amino Acid Sequence, RNA, Messenger, Cells, Cultured
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