title: Tumor suppressor BLU enhances pro-apoptotic activity of sMEK1 through physical interaction.
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.
authors.affiliation: Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Seung Myung
authors.initials: SM
authors.lastname: Dong
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Byun
authors.forename: Boh-Ram
authors.initials: BR
authors.lastname: Kim
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C472720:ZMYND10 protein, human; C573787:PPP4R3A protein, human; D010749:Phosphoprotein Phosphatases