Abstract
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Apoptosis*
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Cell Cycle
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Cell Line, Tumor
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Cells, Cultured
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Cytoskeletal Proteins
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Female
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Gene Expression Regulation, Neoplastic
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HEK293 Cells
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Humans
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Molecular Sequence Data
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism*
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Phosphoprotein Phosphatases / chemistry
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism*
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Protein Interaction Mapping
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA, Messenger / genetics
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / metabolism*
Substances
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Cytoskeletal Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Tumor Suppressor Proteins
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ZMYND10 protein, human
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PPP4R3A protein, human
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Phosphoprotein Phosphatases