NM23-H2 involves in negative regulation of Diva and Bcl2L10 in apoptosis signaling.
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.
Kang
Yeongsup
Y
Graduate School of Life Science and Biotechnology, Pochon CHA University, School of Medicine, Seongnam 463-836, South Korea.
Lee
Deug-Chan
DC
Han
Jiyou
J
Yoon
Seongmin
S
Won
Miae
M
Yeom
Ji-Hyun
JH
Seong
Maeng-Je
MJ
Ko
Jeong-Jae
JJ
Lee
Kyung-Ah
KA
Lee
Kangseok
K
Bae
Jeehyeon
J
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*
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