title: Caspase-7 mediated cleavage of proteasome subunits during apoptosis.
abstract: 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.
authors: Translational Research Center, KRIBB, Daejeon, South Korea.
authors: Mi
authors: M
authors: Jang
authors: Byoung Chul
authors: BC
authors: Park
authors: Ah Young
authors: AY
authors: Lee
authors: Kyeong Sook
authors: KS
authors: Na
authors: Sunghyun
authors: S
authors: Kang
authors: Kwang-Hee
authors: KH
authors: Bae
authors: Pyung Keun
authors: PK
authors: Myung
authors: Bong Chul
authors: BC
authors: Chung
authors: Sayeon
authors: S
authors: Cho
authors: Do Hee
authors: DH
authors: Lee
authors: Sung Goo
authors: SG
authors: Park
mesh_terms: 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*
chemical_list: D021122:Protein Subunits; D025801:Ubiquitin; D053148:Caspase 3; D053179:Caspase 7; D046988:Proteasome Endopeptidase Complex