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更新时间:2025-08-08
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PARP1 possesses a nuclear localization sequence (NLS) near the DNA-binding domain and a caspase-cleavage site between the DNA-binding domain and the automodification domain [PMID: 10455009]. During caspasedependent apoptosis, PARP1 is cleaved by caspases 3 and 7 at its caspase-cleavage site into 24-kDa and 89-kDa fragments [PMID: 10497198, PMID: 8358726]. The 24-kDa PARP1 fragment contains the DNAbinding motif and the NLS, whereas the 89-kDa PARP1 fragment contains the automodification and catalytic domains. After PARP1 cleavage by caspase, the 24-kDa PARP1 fragment irreversibly binds to DNA breaks and acts as a transdominant inhibitor of active PARP1, whereas the 89-kDa PARP1 fragment is translocated to the cytoplasm [PMID: 11570811, PMID: 9721847]. Thereby, PARP1 fragmentation by caspase leads to its inactivation, which inhibits DNA repair and facilitates caspase-mediated DNA fragmentation in apoptosis.