Expansion of a polyglutamine sequence in the N terminus of huntingtin is the gain-of-function event that causes Huntington's disease. This mutation affects primarily the medium-size spiny neurons of the striatum. Huntingtin is expressed in many neuronal and non-neuronal cell types, implying a more general function for the wild-type protein. Here we report that wild-type huntingtin acts by protecting CNS cells from a variety of apoptotic stimuli, including serum withdrawal, death receptors, and pro-apoptotic Bcl-2 homologs. This protection may take place at the level of caspase-9 activation. The full-length protein also modulates the toxicity of the poly-Q expansion. Cells expressing full-length mutant protein are susceptible to fewer death stimuli than cells expressing truncated mutant huntingtin.

Wild-type huntingtin protects from apoptosis upstream of caspase-3 / D. Rigamonti, J.H. Bauer, C. De-Fraja, L. Conti, S. Sipione, C. Sciorati, E. Clementi, A. Hackam, M.R. Hayden, Y. Li, J.K. Cooper, C.A. Ross, S. Govoni, C. Vincenz, E. Cattaneo. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 20:10(2000 May 15), pp. 3705-3713.

Wild-type huntingtin protects from apoptosis upstream of caspase-3

D. Rigamonti;L. Conti;E. Clementi;E. Cattaneo
2000

Abstract

Expansion of a polyglutamine sequence in the N terminus of huntingtin is the gain-of-function event that causes Huntington's disease. This mutation affects primarily the medium-size spiny neurons of the striatum. Huntingtin is expressed in many neuronal and non-neuronal cell types, implying a more general function for the wild-type protein. Here we report that wild-type huntingtin acts by protecting CNS cells from a variety of apoptotic stimuli, including serum withdrawal, death receptors, and pro-apoptotic Bcl-2 homologs. This protection may take place at the level of caspase-9 activation. The full-length protein also modulates the toxicity of the poly-Q expansion. Cells expressing full-length mutant protein are susceptible to fewer death stimuli than cells expressing truncated mutant huntingtin.
Animals ; Apoptosis ; Caspase 3 ; Corpus Striatum ; Caspases ; bcl-X Protein; Nerve Tissue Proteins ; Cell Survival ; Mutagenesis ; Cerebral Cortex ; Proto-Oncogene Proteins c-bcl-2 ; In Situ Nick-End Labeling ; Promoter Regions, Genetic; Caspase 9 ; Gene Expression Regulation, Enzymologic ; Nuclear Proteins ; Transfection ; Neurons ; Cell Line, Transformed
Settore BIO/14 - Farmacologia
http://www.jneurosci.org/content/20/10/3705.long
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/206978
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