Polyglutamine repeat length-dependent proteolysis of huntingtin

Banghua Sun, Wei Fan, Aldona Balciunas, Jillian K. Cooper, Gal Bitan, Shirley Steavenson, Paul E. Denis, Yunjen Young, Beverly Adler, Larry Daugherty, Raffi Manoukian, Gary Elliott, Wenyan Shen, Jane Talvenheimo, David B. Teplow, Mitsuru Haniu, Raj Haldankar, Jette Wypych, Christopher A Ross, Martin CitronWilliam G. Richards

Research output: Contribution to journalArticle

Abstract

Amino-terminal fragments of huntingtin, which contain the expanded polyglutamine repeat, have been proposed to contribute to the pathology of Huntington's disease (HD). Data supporting this claim have been generated from patients with HD in which truncated amino-terminal fragments forming intranuclear inclusions have been observed, and from animal and cell-based models of HD where it has been demonstrated that truncated polyglutamine-containing fragments of htt are more toxic than full-length huntingtin. We report here the identification of a region within huntingtin, spanning from amino acids 63 to 111, that is cleaved in cultured cells to generate a fragment of similar size to those observed in patients with HD. Importantly, proteolytic cleavage within this region appears dependent upon the length of the polyglutamine repeat within huntingtin, with pathological polyglutamine repeat-containing huntingtin being more efficiently cleaved than huntingtin containing polyglutamine repeats of nonpathological size.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalNeurobiology of Disease
Volume11
Issue number1
DOIs
StatePublished - 2002

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Proteolysis
Huntington Disease
Intranuclear Inclusion Bodies
Poisons
Cultured Cells
polyglutamine
Pathology
Amino Acids

ASJC Scopus subject areas

  • Neurology

Cite this

Sun, B., Fan, W., Balciunas, A., Cooper, J. K., Bitan, G., Steavenson, S., ... Richards, W. G. (2002). Polyglutamine repeat length-dependent proteolysis of huntingtin. Neurobiology of Disease, 11(1), 111-122. https://doi.org/10.1006/nbdi.2002.0539

Polyglutamine repeat length-dependent proteolysis of huntingtin. / Sun, Banghua; Fan, Wei; Balciunas, Aldona; Cooper, Jillian K.; Bitan, Gal; Steavenson, Shirley; Denis, Paul E.; Young, Yunjen; Adler, Beverly; Daugherty, Larry; Manoukian, Raffi; Elliott, Gary; Shen, Wenyan; Talvenheimo, Jane; Teplow, David B.; Haniu, Mitsuru; Haldankar, Raj; Wypych, Jette; Ross, Christopher A; Citron, Martin; Richards, William G.

In: Neurobiology of Disease, Vol. 11, No. 1, 2002, p. 111-122.

Research output: Contribution to journalArticle

Sun, B, Fan, W, Balciunas, A, Cooper, JK, Bitan, G, Steavenson, S, Denis, PE, Young, Y, Adler, B, Daugherty, L, Manoukian, R, Elliott, G, Shen, W, Talvenheimo, J, Teplow, DB, Haniu, M, Haldankar, R, Wypych, J, Ross, CA, Citron, M & Richards, WG 2002, 'Polyglutamine repeat length-dependent proteolysis of huntingtin', Neurobiology of Disease, vol. 11, no. 1, pp. 111-122. https://doi.org/10.1006/nbdi.2002.0539
Sun B, Fan W, Balciunas A, Cooper JK, Bitan G, Steavenson S et al. Polyglutamine repeat length-dependent proteolysis of huntingtin. Neurobiology of Disease. 2002;11(1):111-122. https://doi.org/10.1006/nbdi.2002.0539
Sun, Banghua ; Fan, Wei ; Balciunas, Aldona ; Cooper, Jillian K. ; Bitan, Gal ; Steavenson, Shirley ; Denis, Paul E. ; Young, Yunjen ; Adler, Beverly ; Daugherty, Larry ; Manoukian, Raffi ; Elliott, Gary ; Shen, Wenyan ; Talvenheimo, Jane ; Teplow, David B. ; Haniu, Mitsuru ; Haldankar, Raj ; Wypych, Jette ; Ross, Christopher A ; Citron, Martin ; Richards, William G. / Polyglutamine repeat length-dependent proteolysis of huntingtin. In: Neurobiology of Disease. 2002 ; Vol. 11, No. 1. pp. 111-122.
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