title: NM23-H2 involves in negative regulation of Diva and Bcl2L10 in apoptosis signaling.
abstract: The Bcl-2 family members are evolutionally conserved and crucial regulators of apoptosis. Diva (Boo), an ortholog of Bcl2L10 or Bcl-B, is a member of the Bcl-2 family that has contradictory functions in apoptosis. To understand the signaling mechanisms of Diva, we searched for proteins that interact with Diva using the yeast two-hybrid system. We identified a nucleoside diphosphate kinase isoform, NM23-H2. Here, we show that Diva bound to NM23-H2 in cells in which the transmembrane domain of Diva was required, and both proteins were colocalized in cytoplasm. Of interest, Diva protein level was significantly down-regulated by NM23-H2 as knock down of NM23-H2 restored Diva expression. Overexpression of NM23-H2 induced apoptosis, and the depletion of NM23-H2 led to the increase of Diva's apoptotic activity. Thus, these results indicate the existence of a previously undiscovered mechanism by which NM23-H2 involves in the regulation of Diva-mediated apoptosis.
authors.affiliation: Graduate School of Life Science and Biotechnology, Pochon CHA University, School of Medicine, Seongnam 463-836, South Korea.
authors.forename: Yeongsup
authors.initials: Y
authors.lastname: Kang
authors.forename: Deug-Chan
authors.initials: DC
authors.lastname: Lee
authors.forename: Jiyou
authors.initials: J
authors.lastname: Han
authors.forename: Seongmin
authors.initials: S
authors.lastname: Yoon
authors.forename: Miae
authors.initials: M
authors.lastname: Won
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yeom
authors.forename: Maeng-Je
authors.initials: MJ
authors.lastname: Seong
authors.forename: Jeong-Jae
authors.initials: JJ
authors.lastname: Ko
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Lee
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D005246:Feedback / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C117144:BCL2-like 10 protein; D054778:NM23 Nucleoside Diphosphate Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase