Nuclear translocation controlled by alternatively spliced isoforms inactivates the QUAKING apoptotic inducer
Abstract
The quaking viable mice have myelination defects and develop a characteristic tremor 10 d after birth. The quaking gene encodes at least five alternatively spliced QUAKING (QKI) isoforms that differ in their C-terminal 8–30-amino-acid sequence. The reason for the existence of the different QKI isoforms and their function are unknown. Here we show that only one QKI isoform, QKI-7, can induce apoptosis in fibroblasts and primary rat oligodendrocytes. Heterodimerization of the QKI isoforms results in the nuclear translocation of QKI-7 and the suppression of apoptosis. The unique C-terminal 14 amino acids of QKI-7 confers the ability to induce apoptosis to heterologous proteins such as the green fluorescent protein and a QKI-related protein, Caenorhabditis elegansGLD-1. Thus, the unique C-terminal sequences of QKI-7 may function as a life-or-death ‘sensor’ that monitors the balance between the alternatively spliced QKI isoforms. Moreover, our findings suggest that nuclear translocation is a novel mechanism of inactivating apoptotic inducers.
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Footnotes
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↵1 Corresponding author.
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E-MAIL sricha{at}po-box.mcgill.ca; FAX (514) 340-8295.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.860301.
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- Received October 9, 2000.
- Accepted January 31, 2001.
- Cold Spring Harbor Laboratory Press