Unknown

Dataset Information

0

Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117.


ABSTRACT: Deubiquitinating enzymes (DUbs) play important roles in many ubiquitin-dependent pathways, yet how DUbs themselves are regulated is not well understood. Here, we provide insight into the mechanism by which ubiquitination directly enhances the activity of ataxin-3, a DUb implicated in protein quality control and the disease protein in the polyglutamine neurodegenerative disorder, Spinocerebellar Ataxia Type 3. We identify Lys-117, which resides near the catalytic triad, as the primary site of ubiquitination in wild type and pathogenic ataxin-3. Further studies indicate that ubiquitin-dependent activation of ataxin-3 at Lys-117 is important for its ability to reduce high molecular weight ubiquitinated species in cells. Ubiquitination at Lys-117 also facilitates the ability of ataxin-3 to induce aggresome formation in cells. Finally, structure-function studies support a model of activation whereby ubiquitination at Lys-117 enhances ataxin-3 activity independent of the known ubiquitin-binding sites in ataxin-3, most likely through a direct conformational change in or near the catalytic domain.

SUBMITTER: Todi SV 

PROVIDER: S-EPMC2998082 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

altmetric image

Publications

Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117.

Todi Sokol V SV   Scaglione K Matthew KM   Blount Jessica R JR   Basrur Venkatesha V   Conlon Kevin P KP   Pastore Annalisa A   Elenitoba-Johnson Kojo K   Paulson Henry L HL  

The Journal of biological chemistry 20101013 50


Deubiquitinating enzymes (DUbs) play important roles in many ubiquitin-dependent pathways, yet how DUbs themselves are regulated is not well understood. Here, we provide insight into the mechanism by which ubiquitination directly enhances the activity of ataxin-3, a DUb implicated in protein quality control and the disease protein in the polyglutamine neurodegenerative disorder, Spinocerebellar Ataxia Type 3. We identify Lys-117, which resides near the catalytic triad, as the primary site of ubi  ...[more]

Similar Datasets

| S-EPMC2646149 | biostudies-literature
| S-EPMC2546540 | biostudies-literature
| S-EPMC6769291 | biostudies-literature
| S-EPMC9726926 | biostudies-literature
| S-EPMC2064388 | biostudies-literature
| S-EPMC8738964 | biostudies-literature
| S-EPMC7139964 | biostudies-literature
| S-EPMC4668950 | biostudies-literature
| S-EPMC3249107 | biostudies-literature
| S-EPMC5648756 | biostudies-literature