Barbara A Malynn

Conghui Cao, Xue Fu and Xiaoli Wang* Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission (NHC) Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China Background: Haploinsufficiency of A20 (HA20) is a monogenic autosomal-dominant genetic autoinflammatory disease caused by loss of function mutations in the TNFAIP3 gene.

Abstract A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20’s zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20’s OTU or ZF4 motifs did not exhibit this phenotype.

OTUB1 is a deubiquitinating enzyme that cleaves Lys48-linked polyubiquitin chains and also regulates ubiquitin signaling through a unique, non-catalytic mechanism. OTUB1 binds to a subset of E2 ubiquitin conjugating enzymes and inhibits their activity by trapping the E2~ubiquitin thioester and preventing ubiquitin transfer. The same set of E2s stimulate the deubiquitinating activity of OTUB1 when the E2 is not charged with ubiquitin.