E2 Partner Tunes the Ubiquitylation Specificity of Arkadia E3 Ubiquitin Ligase.

Arkadia () is a positive regulator of the TGF- signaling that mediates the proteasome-dependent degradation of negative factors of the pathway. It is classified as an E3 ubiquitin ligase and a SUMO-targeted ubiquitin ligase (STUBL), implicated in various pathological conditions including cancer and fibrosis. The enzymatic (ligase) activity of Arkadia is located at its C-terminus and involves the RING domain.

Unveiling the Essential Role of Arkadia's Non-RING Elements in the Ubiquitination Process.

Arkadia is a positive regulator of the TGF-SMAD2/3 pathway, acting through its C-terminal RING-H2 domain and targeting for degradation of its negative regulators. Here we explore the role of regions outside the RING domain (non-RING elements) of Arkadia on the E2-E3 interaction. The contribution of the non-RING elements was addressed using Arkadia RING 68 aa and Arkadia 119 aa polypeptides.