Affordable Access

A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy.

Authors
  • Young, Philip J
  • Day, Patricia M
  • Zhou, Jianhua
  • Androphy, Elliot J
  • Morris, Glenn E
  • Lorson, Christian L
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
Jan 25, 2002
Volume
277
Issue
4
Pages
2852–2859
Identifiers
PMID: 11704667
Source
Medline
License
Unknown

Abstract

Mutations in the SMN1 (survival motor neuron 1) gene cause spinal muscular atrophy (SMA). We now show that SMN protein, the SMN1 gene product, interacts directly with the tumor suppressor protein, p53. Pathogenic missense mutations in SMN reduce both self-association and p53 binding by SMN, and the extent of the reductions correlate with disease severity. The inactive, truncated form of SMN produced by the SMN2 gene in SMA patients fails to bind p53 efficiently. SMN and p53 co-localize in nuclear Cajal bodies, but p53 redistributes to the nucleolus in fibroblasts from SMA patients. These results suggest a functional interaction between SMN and p53, and the potential for apoptosis when this interaction is impaired may explain motor neuron death in SMA.

Report this publication

Statistics

Seen <100 times