کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1929766 | 1050473 | 2012 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase](/preview/png/1929766.png)
Autosomal dominant mutations in BTB and Kelch domain containing 13 protein (KBTBD13) are associated with a new type of Nemaline Myopathy (NEM). NEM is a genetically heterogeneous group of muscle disorders. Mutations causing phenotypically distinct NEM variants have previously been identified in components of muscle thin filament. KBTBD13 is a muscle specific protein composed of an N terminal BTB domain and a C terminal Kelch-repeat domain. The function of this newly identified protein in muscle remained unknown. In this study, we show that KBTBD13 interacts with Cullin 3 (Cul3) and the BTB domain mediates this interaction. Using ubiquitination assays, we determined that KBTBD13 participates in the formation of a Cul3 based RING ubiquitin ligase (Cul3-RL) capable of ubiquitin conjugation. Confocal microscopy of transiently expressed KBTBD13 revealed its co-localization with ubiquitin. Taken together, our results demonstrate that KBTBD13 is a putative substrate adaptor for Cul3-RL that functions as a muscle specific ubiquitin ligase, and thereby implicate the ubiquitin proteasome pathway in the pathogenesis of KBTBD13-associated NEM.
► BTB and Kelch domain containing 13 protein (KBTBD13) interacts with Cullin 3 (Cul3).
► The BTB domain of KBTBD13 is necessary and sufficient for binding to Cul3.
► KBTBD13 forms a functional complex with Cul3 RING ubiquitin ligase.
► Ubiquitin proteasome pathway is suggested as the mechanism for KBTBD13-associated Nemaline Myopathy.
Journal: Biochemical and Biophysical Research Communications - Volume 421, Issue 4, 18 May 2012, Pages 743–749