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Type: Journal article
Title: Role of prodomain in importin-mediated nuclear localization and activation of caspase-2
Author: Baliga, B.
Colussi, P.
Read, S.
Dias, M.
Jans, D.
Kumar, S.
Citation: Journal of Biological Chemistry, 2003; 278(7):4899-4905
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2003
ISSN: 0021-9258
Statement of
Belinda C. Baliga, Paul A. Colussi, Stuart H. Read, Manisha M. Dias, David A. Jans, and Sharad Kumar
Abstract: 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.
Keywords: COS Cells
3T3 Cells
Cell Nucleus
Protein Precursors
Recombinant Proteins
Enzyme Activation
Amino Acid Sequence
Protein Structure, Tertiary
Protein Transport
Molecular Sequence Data
Caspase 2
Provenance: Published online ahead of print December 10, 2002
Rights: © 2002 by the American Society for Biochemistry and Molecular Biology.
DOI: 10.1074/jbc.M211512200
Appears in Collections:Aurora harvest 4
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