ArticleThe Journal of biological chemistry2011
A novel degradation signal derived from distal C-terminal frameshift mutations of KCNQ2 protein which cause neonatal epilepsy.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Reduced axonal surface expression and phosphoinositide sensitivity in KNeurobiology of disease · 2018Article
- Degradation Signals for Ubiquitin-Proteasome Dependent Cytosolic Protein Quality Control (CytoQC) in Yeast.G3 (Bethesda, Md.) · 2016Article
- Proteins directly interacting with mammalian 20S proteasomal subunits and ubiquitin-independent proteasomal degradation.Biomolecules · 2014Review
- Voltage-gated potassium channels at the crossroads of neuronal function, ischemic tolerance, and neurodegeneration.Translational stroke research · 2014Review
- Cardiovascular responses to retigabine in conscious rats--under normotensive and hypertensive conditions.British journal of pharmacology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Benign familial neonatal convulsions is an autosomal-dominant idiopathic form of epilepsy primarily caused by gene mutations of the voltage-gated Kv7.2/KCNQ2/M-channel that exert only partial dominant-negative effects. However, the mechanism underlying the incomplete dominance of channel mutations, which cause epilepsy in infancy, remains unknown. Using mutagenesis and biochemistry combined with electrophysiology, we identified a novel degradation signal derived from distal C-terminal frameshift mutations, which impairs channel function. This degradation signal, transferable to non-channel CD4, can lead to accelerated degradation of mutant proteins through ubiquitin-independent proteasome machinery but does not affect mRNA quantity and protein trafficking. Functional dissection of this signal has revealed a key five-amino acid (RCXRG) motif critical for degradation. Taken together, our findings reveal a mechanism by which proteins that carry this signal are subject to degradation, leading to M-current dysfunction, which causes epilepsy.
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