Document Detail

Involvement of survival motor neuron (SMN) protein in cell death.
MedLine Citation:
PMID:  12374765     Owner:  NLM     Status:  MEDLINE    
Infantile spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN)1 gene. We investigated the role of human (h) SMN protein on cell death in PC12 and Rat-1 cells. hSMN prolonged cell survival in PC12 cells deprived of trophic support and in Rat-1 cells induced to die by activation of the proto-oncogene c-Myc, to similar magnitude as Bcl-2 or IAP-2. While hSMN was ineffective in inhibiting apoptosis induced by ultraviolet light (UV) or etoposide treatment in proliferating PC12 or Rat-1 cells, a protective effect was observed in terminally NGF/dBcAMP-differentiated PC12 cells. hSMN inhibited the onset of apoptosis in NGF/dBcAMP-deprived or UV-treated co-differentiated PC12 cells by preventing cytochrome c release and caspase-3 activation, indicating that its effects are through suppression of the mitochondrial apoptotic pathway. Expressing hSMN deleted for exon 7 (Delta7) or for exons 6 and 7 (Delta6/7), or with the SMA point mutant Y272C, resulted in loss of survival function. Moreover, these mutants also exhibited pro-apoptotic effects in Rat-1 cells. The localization pattern of full-length hSMN in PC12 and Rat-1 cells was similar to that of endogenous SMN: granular labelling in the cytoplasm and discrete fluorescence spots in the nucleus, some of which co-localized with p80 coilin, the characteristic marker of Cajal bodies. However, cytoplasmic and nuclear aggregates were often seen with hSMNDelta7, whereas the hSMNDelta6/7 mutant showed homogenous nuclear labelling that excluded the nucleolus. Thus, our results show that the C-terminal region is critical in suppression of apoptosis by SMN.
Sheela Vyas; Catherine Béchade; Béatrice Riveau; Julian Downward; Antoine Triller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human molecular genetics     Volume:  11     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-10     Completed Date:  2003-03-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  2751-64     Citation Subset:  IM    
INSERM U497, 46 rue d'Ulm, Paris 75005, France.
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MeSH Terms
Apoptosis / drug effects,  genetics,  physiology*,  radiation effects
Caspase 3
Caspases / metabolism
Cell Differentiation
Cell Line
Cyclic AMP Response Element-Binding Protein
Cytochrome c Group / metabolism
DNA Damage
Etoposide / pharmacology
Genes, myc
Motor Neurons / metabolism,  pathology
Nerve Tissue Proteins / genetics,  physiology*
PC12 Cells
RNA-Binding Proteins
Recombinant Proteins / genetics,  metabolism
SMN Complex Proteins
Spinal Muscular Atrophies of Childhood / genetics,  pathology
Survival of Motor Neuron 1 Protein
Ultraviolet Rays
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Cytochrome c Group; 0/Nerve Tissue Proteins; 0/RNA-Binding Proteins; 0/Recombinant Proteins; 0/SMN Complex Proteins; 0/Smn1 protein, rat; 0/Survival of Motor Neuron 1 Protein; 33419-42-0/Etoposide; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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