Neurobiology of Disease (Oct 2002)
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 Citron,
- William G. Richards
Affiliations
- Banghua Sun
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Wei Fan
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Aldona Balciunas
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Jillian K. Cooper
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Gal Bitan
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Shirley Steavenson
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Paul E. Denis
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Yunjen Young
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Beverly Adler
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Larry Daugherty
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Raffi Manoukian
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Gary Elliott
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Wenyan Shen
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Jane Talvenheimo
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- David B. Teplow
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Mitsuru Haniu
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Raj Haldankar
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Jette Wypych
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Christopher A. Ross
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Martin Citron
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- William G. Richards
- Amgen Inc. Thousand Oaks, California, 91320; Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts, 02115
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 111 – 122
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.
