Disease-associated variants of microsomal retinol dehydrogenase 12 (RDH12) are degraded at mutant-specific rates.

Abstract:

:Mutations in retinol dehydrogenase 12 (RDH12) cause severe retinal degeneration. However, some of the disease-associated RDH12 mutants retain significant catalytic activity, indicating the existence of additional pathophysiological mechanisms. This study demonstrates that the catalytically active T49M and I51N mutants undergo accelerated degradation, which results in their reduced cellular levels. Inhibition of proteasome leads to significant accumulation of ubiquitylated T49M and I51N. Furthermore, the degree of ubiquitylation strongly correlates with the half-lives of the proteins. These results suggest that the accelerated degradation of RDH12 mutants by the ubiquitin-proteasome system contributes to the pathophysiology and phenotypic variability associated with mutations in the RDH12 gene.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Lee SA,Belyaeva OV,Kedishvili NY

doi

10.1016/j.febslet.2009.12.009

subject

Has Abstract

pub_date

2010-02-05 00:00:00

pages

507-10

issue

3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(09)01055-2

journal_volume

584

pub_type

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