Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth
Copyright policy )Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth
The destruction of cellular targets during apoptosis is carried out by caspases, which are negatively regulated by the inhibitor of apoptosis proteins (IAP); however, death effector domain (DED) caspases of the extrinsic pathway are refractory to the IAP family. We have isolated a family of apoptotic inhibitors [caspases-8- and -10-associated RING proteins (CARPs)] that bind to and negatively regulate DED caspases. When overexpressed, CARPs, via an IAP-like RING domain, can contribute to the ubiquitin-mediated proteolysis of DED caspases. Furthermore, CARPs are rapidly cleaved during apoptosis. However, in tumors and tumor cell lines, they are overexpressed, and their silencing leads to restoration of efficient apoptosis via enhanced activation of DED caspases. Long-term inhibition of CARP expression results in suppression of cancer cell growth, highlighting their importance in tumor cell survival.
- University of Pennsylvania United States
- Howard Hughes Medical Institute United States
Sequence Homology, Amino Acid, Hydrolysis, Molecular Sequence Data, Cell Cycle Proteins, Nerve Tissue Proteins, Ligands, Cell Line, Tumor, Humans, Amino Acid Sequence, Cloning, Molecular, RNA, Small Interfering, Apoptosis Regulatory Proteins, Carrier Proteins, Cell Division, Phospholipids
Sequence Homology, Amino Acid, Hydrolysis, Molecular Sequence Data, Cell Cycle Proteins, Nerve Tissue Proteins, Ligands, Cell Line, Tumor, Humans, Amino Acid Sequence, Cloning, Molecular, RNA, Small Interfering, Apoptosis Regulatory Proteins, Carrier Proteins, Cell Division, Phospholipids
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