SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery.

ABSTRACT:

Background

Mutations in the Fe-S cluster-containing SDHB subunit of succinate dehydrogenase cause familial cancer syndromes. Recently the tripeptide motif L(I)YR was identified in the Fe-S recipient protein SDHB, to which the cochaperone HSC20 binds.

Methods

In order to characterize the metabolic basis of SDH-deficient cancers we performed stable isotope-resolved metabolomics in a novel SDHB-deficient renal cell carcinoma cell line and conducted bioinformatics and biochemical screening to analyze Fe-S cluster acquisition and assembly of SDH in the presence of other cancer-causing SDHB mutations.

Results

We found that the SDHBR46Q mutation in UOK269 cells disrupted binding of HSC20, causing rapid degradation of SDHB. In the absence of SDHB, respiration was undetectable

SUBMITTER: Saxena N 

PROVIDER: S-EPMC4732025 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature