TY - JOUR T1 - Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase-3 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3705 LP - 3713 DO - 10.1523/JNEUROSCI.20-10-03705.2000 VL - 20 IS - 10 AU - Dorotea Rigamonti AU - Johannes H. Bauer AU - Claudio De-Fraja AU - Luciano Conti AU - Simonetta Sipione AU - Clara Sciorati AU - Emilio Clementi AU - Abigail Hackam AU - Michael R. Hayden AU - Yong Li AU - Jillian K. Cooper AU - Christopher A. Ross AU - Stefano Govoni AU - Claudius Vincenz AU - Elena Cattaneo Y1 - 2000/05/15 UR - http://www.jneurosci.org/content/20/10/3705.abstract N2 - 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. ER -