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.
|Titolo:||Wild-type huntingtin protects from apoptosis upstream of caspase-3|
|Parole Chiave:||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 Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||15-mag-2000|
|Appare nelle tipologie:||01 - Articolo su periodico|