Differential localization of ICAD-L and ICAD-S in cells due to removal of a C-terminal NLS from ICAD-L by alternative splicing |
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Authors: | Samejima K Earnshaw W C |
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Institution: | Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh, Scotland, EH9 3JR, United Kingdom. |
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Abstract: | CAD/CPAN/DFF40 is an apoptotic nuclease that is associated with the regulatory subunit ICAD/DFF in healthy cells. ICAD has two forms, ICAD-L/DFF45 and ICAD-S/DFF35, which are transcribed from a single gene by alternative splicing. They differ at the C-terminus: 70 amino acids of ICAD-L are replaced by 4 different amino acids in ICAD-S. We previously showed that both transfected and endogenous ICAD-L are nuclear; however, the localization of ICAD and CAD remains controversial and an important issue to clarify. Here we present the evidence that ICAD-L is nuclear due to the presence of an autonomous nuclear localization signal located in the C-terminal 20 amino acids. This NLS is missing from ICAD-S, which is distributed throughout the cell. We also showed that a GFP:CAD fusion protein is located in the nucleus of transfected cells. |
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Keywords: | apoptosis ICAD-L ICAD-S CAD |
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