| First Author | Baliga BC | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 7 | Pages | 4899-905 |
| PubMed ID | 12477715 | Mgi Jnum | J:81904 |
| Mgi Id | MGI:2450211 | Doi | 10.1074/jbc.M211512200 |
| Citation | Baliga BC, et al. (2003) Role of Prodomain in Importin-mediated Nuclear Localization and Activation of Caspase-2. J Biol Chem 278(7):4899-905 |
| abstractText | Caspase-2 is unique among mammalian caspases because it localizes to the nucleus in a prodomain-dependent manner. The caspase-2 prodomain also regulates caspase-2 activity via a caspase recruitment domain that mediates oligomerization of procaspase-2 molecules and their subsequent autoactivation. In this study we sought to map specific functional regions in the caspase-2 prodomain that regulate its nuclear transport and also its activation. Our data indicate that caspase-2 contains a classical nuclear localization signal (NLS) at the C terminus of the prodomain which is recognized by the importin alpha/beta heterodimer. The mutation of a conserved Lys residue in the NLS abolishes nuclear localization of caspase-2 and binding to the importin alpha/beta heterodimer. Although caspase-2 is imported into the nucleus, mutants lacking the NLS were still capable of inducing apoptosis upon overexpression in transfected cells. We define a region in the prodomain that regulates the ability of caspase-2 to form dot- and filament-like structures when ectopically expressed, which in turn promotes cell killing. Our data provides a mechanism for caspase-2 nuclear import and demonstrate that association of procaspase-2 into higher order structures, rather than its nuclear localization, is required for caspase-2 activation and its ability to induce apoptosis. |
