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PMID: 11297509 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 15 ·No. 7 ·2001-04-01 ·Pages 845-58

Pilotte J, Larocque D, Richard S

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 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.

MeSH Terms
3T3 Cells/cytology Adenoviridae/genetics Alternative Splicing Amino Acid Sequence Animals Apoptosis/genetics,physiology Cell Nucleus/metabolism Cells, Cultured Demyelinating Diseases Dimerization Genetic Vectors/genetics HeLa Cells Humans Mice Mice, Quaking Molecular Sequence Data Oligodendroglia/cytology Protein Isoforms/chemistry,genetics,physiology Protein Multimerization Protein Sorting Signals/physiology Protein Transport RNA-Binding Proteins/chemistry,genetics,physiology Rats Recombinant Fusion Proteins/physiology Sequence Alignment Structure-Activity Relationship Tetracycline/pharmacology Transcriptional Activation/drug effects Transfection
Chemicals
Protein Isoforms Protein Sorting Signals QKI protein, human Qk protein, mouse RNA-Binding Proteins Recombinant Fusion Proteins Tetracycline
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pilotte J
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, Montréal, Québec, H3T 1E2, Canada.
Larocque D
Richard S
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.860301
Published
2001-04-01
Pages
845-58
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312664
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.860301 PMC Full Text View journal details
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