Caspase 3 activation is controlled by a sequence located in the N-terminus of its large subunit.
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Pelletier M, Cartron PF, Delaval F, Meflah K, Vallette FM, Oliver L
Caspase 3 activation is controlled by a sequence located in the N-terminus of its large subunit.
Biochem Biophys Res Commun. 2004 Mar 26;316(1):93-9.
- PubMed ID
- 15003516 [ View in PubMed]
- Abstract
We report that the induction and completion of the apoptotic program is delayed in a doxorubicin-resistant cell line (HL60/ADR). This hindrance to cell death occurred downstream of the multidrug-resistant protein (mrp), a transmembrane transporter. In vitro studies showed that these cells were incapable of correctly activating procaspase 3 (pC3), the main executioner of apoptosis. Sequencing of HL60/ADR pC3 revealed point mutations in a sequence located in the N-terminal region of the large subunit of caspase 3 (C3, amino acids 31-37; i.e., immediately after the propeptide). We called this particular form of C3, the C3 N-terminal modified (C3-NTM), and show that it is partially active when transfected into MCF-7 cells shown to have little or no endogenous pC3. As a deletion of the amino acids 31-37 in wild-type C3 leads to the same phenotype, we conclude that this sequence is involved in C3 activation during apoptosis.