Caspase-7 mediated cleavage of proteasome subunits during apoptosis.
Caspase-3 and caspase-7 are structurally closely related and demonstrate overlapping substrate specificity. However, during apoptosis, they are differentially regulated and show distinct subcellular localizations, implying the presence of specific substrates. In this study, to identify caspase-7 substrates, we treated the lysates derived from caspase-3-deficient MCF-7 cells with purified caspase-7 and analyzed decreased proteins by 2-DE. Intriguingly, several proteasome subunits such as alpha2, alpha6, and Rpt1 are degraded by caspase-7 during apoptosis in vitro and in vivo. Caspase-7 mediated cleavage of proteasome subunits results in the reduction of proteasome activity and thereby increases the accumulation of ubiquitinated proteins in cells. These findings suggest that caspase-7 facilitates the execution of apoptosis through down-regulation of the 26S proteasome, which regulates the turnover of proteins involved in the apoptotic process.
Jang
Mi
M
Translational Research Center, KRIBB, Daejeon, South Korea.
Park
Byoung Chul
BC
Lee
Ah Young
AY
Na
Kyeong Sook
KS
Kang
Sunghyun
S
Bae
Kwang-Hee
KH
Myung
Pyung Keun
PK
Chung
Bong Chul
BC
Cho
Sayeon
S
Lee
Do Hee
DH
Park
Sung Goo
SG
D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits; D025801:Ubiquitin / Q000378:metabolism*
D021122:Protein Subunits; D025801:Ubiquitin; D053148:Caspase 3; D053179:Caspase 7; D046988:Proteasome Endopeptidase Complex