UBASH3A Mediates Risk for Type 1 Diabetes Through Inhibition of T-Cell Receptor-Induced NF-κB Signaling.

ABSTRACT: Although over 40 type 1 diabetes (T1D) risk loci have been mapped in humans, the causative genes and variants for T1D are largely unknown. Here, we investigated a candidate gene in the 21q22.3 risk locus-UBASH3A, which is primarily expressed in T cells where it is thought to play a largely redundant role. Genetic variants in UBASH3A have been shown to be associated with several autoimmune diseases in addition to T1D. However, the molecular mechanism underlying these genetic associations is unresolved. Our study reveals a previously unrecognized role of UBASH3A in human T cells: UBASH3A attenuates the NF-κB signal transduction upon T-cell receptor (TCR) stimulation by specifically suppressing the activation of the IκB kinase complex. We identify novel interactions of UBASH3A w

SUBMITTER: Ge Y 

PROVIDER: S-EPMC5482087 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature