Hip2 interacts with and destabilizes Smac/DIABLO.
Hip2 is a ubiquitin-conjugating enzyme that is involved in the cell cycle and suppression of cell death. To understand its role further, we tried to identify proteins that interact with Hip2. Using the immunoprecipitation technique and one-dimensional gel electrophoresis, we identified Smac/DIABLO, a proapoptotic molecule, as a protein that interacts with Hip2. The interaction of Hip2 and Smac was confirmed through in vivo and in vitro experiments. Hip2 promoted degradation of mature Smac through the ubiquitin proteasome pathway. As a result, Hip2 significantly blocked cell death induced by staurosporine and Smac. This study suggests that Hip2 might be involved in the regulation of Smac-mediated apoptosis.
Bae
Yoonhee
Y
Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Kho
Chang Won
CW
Lee
Soo Young
SY
Rhim
Hyangshuk
H
Kang
Seongman
S
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D055550:Protein Stability; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; C100879:UBE2K protein, human; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex