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

Philip J. Young, Patricia M. Day, Jianhua Zhou, Elliot Androphy, Glenn E. Morris, Christian L. Lorson

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 colocalize 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.

Original languageEnglish (US)
Pages (from-to)2852-2859
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number4
DOIs
StatePublished - Jan 25 2002
Externally publishedYes

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Spinal Muscular Atrophy
Motor Neurons
Neurons
Genes
Survival of Motor Neuron 1 Protein
Tumor Suppressor Protein p53
Proteins
Fibroblasts
Missense Mutation
Association reactions
Apoptosis
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy. / Young, Philip J.; Day, Patricia M.; Zhou, Jianhua; Androphy, Elliot; Morris, Glenn E.; Lorson, Christian L.

In: Journal of Biological Chemistry, Vol. 277, No. 4, 25.01.2002, p. 2852-2859.

Research output: Contribution to journalArticle

Young, Philip J. ; Day, Patricia M. ; Zhou, Jianhua ; Androphy, Elliot ; Morris, Glenn E. ; Lorson, Christian L. / A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 4. pp. 2852-2859.
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