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.File | Dimensione | Formato | |
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