| First Author | Scaglione KM | Year | 2011 |
| Journal | Mol Cell | Volume | 43 |
| Issue | 4 | Pages | 599-612 |
| PubMed ID | 21855799 | Mgi Jnum | J:183193 |
| Mgi Id | MGI:5318000 | Doi | 10.1016/j.molcel.2011.05.036 |
| Citation | Scaglione KM, et al. (2011) Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Mol Cell 43(4):599-612 |
| abstractText | The mechanisms by which ubiquitin ligases are regulated remain poorly understood. Here we describe a series of molecular events that coordinately regulate CHIP, a neuroprotective E3 implicated in protein quality control. Through their opposing activities, the initiator E2, Ube2w, and the specialized deubiquitinating enzyme (DUB), ataxin-3, participate in initiating, regulating, and terminating the CHIP ubiquitination cycle. Monoubiquitination of CHIP by Ube2w stabilizes the interaction between CHIP and ataxin-3, which through its DUB activity limits the length of chains attached to CHIP substrates. Upon completion of substrate ubiquitination, ataxin-3 deubiquitinates CHIP, effectively terminating the reaction. Our results suggest that functional pairing of E3s with ataxin-3 or similar DUBs represents an important point of regulation in ubiquitin-dependent protein quality control. In addition, the results shed light on disease pathogenesis in SCA3, a neurodegenerative disorder caused by polyglutamine expansion in ataxin-3. |
