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Genes & Dev. 15 (7): 845-858

Copyright © 2001 by Cold Spring Harbor Laboratory Press.

Vol. 15, No. 7, pp. 845-858, April 1, 2001

Nuclear translocation controlled by alternatively spliced isoforms inactivates the QUAKING apoptotic inducer

Julie Pilotte, Daniel Larocque, and Stéphane Richard1

Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Departments of Oncology, Medicine, Microbiology and Immunology, McGill University, Montréal, Québec, H3T 1E2, Canada

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 elegans GLD-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.

[Key Words: quaking; QKI; nuclear translocation; apoptosis; alternative splicing]

1 Corresponding author.

GENES & DEVELOPMENT 15:845-858 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00

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