Tumor suppressor BLU enhances pro-apoptotic activity of sMEK1 through physical interaction

Cell Signal. 2012 Jun;24(6):1208-14. doi: 10.1016/j.cellsig.2012.02.002. Epub 2012 Feb 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • Cell Cycle
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Molecular Sequence Data
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Interaction Mapping
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / genetics
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*


  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • ZMYND10 protein, human
  • PPP4R3A protein, human
  • Phosphoprotein Phosphatases