Linked Life Data

9389483

Source:http://linkedlifedata.com/resource/pubmed/id/9389483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6658
pubmed:dateCreated
1997-12-19
pubmed:abstractText
Spinal muscular atrophy (SMA) is a motor neuron disease characterized by degeneration of the anterior horn cells of the spinal cord. It is a common fatal autosomal recessive disorder and linkage studies have identified two candidate genes, SMN and NAIP, both on chromosome 5q13. Although NAIP protein is known to have an anti-apoptotic function, the function of SMN has been unclear and it shows no significant sequence similarity to any other protein. The SMN gene is deleted or interrupted on both chromosomes in nearly all SMA patients. Here we show that SMN interacts with Bcl-2, another anti-apoptotic protein, and that co-expression of SMN with Bcl-2 confers a synergistic preventive effect against Bax-induced or Fas-mediated apoptosis, although SMN itself has only a weak anti-apoptotic activity. SMN(Y272C), which carries a missense mutation and was found in an SMA patient who exceptionally retained SMN on one allele, exerts no synergism with Bcl-2. Furthermore, the product of a truncated transcript lacking exon 7, which was derived from an SMN gene carrying an intragenic mutation or from the SMN copy gene cBCD541 retained in all SMA patients, had no synergistic activity but instead had a dominant-negative effect on full-length SMN. Our results indicate that an absent or decreased anti-apoptotic activity of SMN in concert with Bcl-2 underlies the pathogenesis of SMA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
390
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
413-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy.
pubmed:affiliation
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't