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

Dorotea Rigamonti, Johannes H. Bauer, Claudio De-Fraja, Luciano Conti, Simonetta Sipione, Clara Sciorati, Emilio Clementi, Abigail Hackam, Michael R. Hayden, Yong Li, Jillian K. Cooper, Christopher A Ross, Stefano Govoni, Claudius Vincenz, Elena Cattaneo

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3705-3713
Number of pages9
JournalJournal of Neuroscience
Volume20
Issue number10
StatePublished - May 15 2000

Fingerprint

Caspase 3
Apoptosis
Death Domain Receptors
Caspase 9
Huntington Disease
Mutant Proteins
Proteins
Cell Death
Neurons
Mutation
Serum
polyglutamine

Keywords

  • CAG
  • Caspases
  • CNS cells
  • Huntingtin
  • Huntington's disease
  • Survival

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rigamonti, D., Bauer, J. H., De-Fraja, C., Conti, L., Sipione, S., Sciorati, C., ... Cattaneo, E. (2000). Wild-type huntingtin protects from apoptosis upstream of caspase-3. Journal of Neuroscience, 20(10), 3705-3713.

Wild-type huntingtin protects from apoptosis upstream of caspase-3. / Rigamonti, Dorotea; Bauer, Johannes H.; De-Fraja, Claudio; Conti, Luciano; Sipione, Simonetta; Sciorati, Clara; Clementi, Emilio; Hackam, Abigail; Hayden, Michael R.; Li, Yong; Cooper, Jillian K.; Ross, Christopher A; Govoni, Stefano; Vincenz, Claudius; Cattaneo, Elena.

In: Journal of Neuroscience, Vol. 20, No. 10, 15.05.2000, p. 3705-3713.

Research output: Contribution to journalArticle

Rigamonti, D, Bauer, JH, De-Fraja, C, Conti, L, Sipione, S, Sciorati, C, Clementi, E, Hackam, A, Hayden, MR, Li, Y, Cooper, JK, Ross, CA, Govoni, S, Vincenz, C & Cattaneo, E 2000, 'Wild-type huntingtin protects from apoptosis upstream of caspase-3', Journal of Neuroscience, vol. 20, no. 10, pp. 3705-3713.
Rigamonti D, Bauer JH, De-Fraja C, Conti L, Sipione S, Sciorati C et al. Wild-type huntingtin protects from apoptosis upstream of caspase-3. Journal of Neuroscience. 2000 May 15;20(10):3705-3713.
Rigamonti, Dorotea ; Bauer, Johannes H. ; De-Fraja, Claudio ; Conti, Luciano ; Sipione, Simonetta ; Sciorati, Clara ; Clementi, Emilio ; Hackam, Abigail ; Hayden, Michael R. ; Li, Yong ; Cooper, Jillian K. ; Ross, Christopher A ; Govoni, Stefano ; Vincenz, Claudius ; Cattaneo, Elena. / Wild-type huntingtin protects from apoptosis upstream of caspase-3. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 10. pp. 3705-3713.
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