Mevalonate kinase deficiency leads to decreased prenylation of Rab GTPases.

ABSTRACT: Mevalonate kinase deficiency (MKD) is caused by mutations in a key enzyme of the mevalonate-cholesterol biosynthesis pathway, leading to recurrent autoinflammatory disease characterised by enhanced release of interleukin-1β (IL-1β). It is currently believed that the inflammatory phenotype of MKD is triggered by temperature-sensitive loss of mevalonate kinase activity and reduced biosynthesis of isoprenoid lipids required for the prenylation of small GTPase proteins. However, previous studies have not clearly shown any change in protein prenylation in patient cells under normal conditions. With lymphoblast cell lines from two compound heterozygous MKD patients, we used a highly sensitive in vitro prenylation assay, together with quantitative mass spectrometry, to reveal a subtle accumulatio

SUBMITTER: Jurczyluk J 

PROVIDER: S-EPMC5122740 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature