Emergence of the A20/ABIN-mediated inhibition of NF-?B signaling via modifying the ubiquitinated proteins in a basal chordate.

ABSTRACT: In the past decade, ubiquitination has been well documented to have multifaceted roles in regulating NF-?B activation in mammals. However, its function, especially how deubiquitinating enzymes balance the NF-?B activation, remains largely elusive in invertebrates. Investigating bbtA20 and its binding proteins, bbt A20-binding inhibitor of NF-?B (bbtABIN1) and bbtABIN2, in Chinese amphioxus Branchiostoma belcheri tsingtauense, we found that bbtABIN2 can colocalize and compete with bbt TNF receptor-associated factor 6 to connect the K63-linked polyubiquitin chains, whereas bbtABIN1 physically links bbtA20 to bbt NF-?B essential modulator (bbtNEMO) to facilitate the K48-linked ubiquitination of bbtNEMO. Similar to human A20, bbtA20 is a dual enzyme that removes the K63-linked polyubiquitin chains and builds the K48-linked polyubiquitin chains on bbt receptor-interacting serine/threonine protein kinase 1b, leading to the inhibition of NF-?B signaling. Our study not only suggests that ubiquitination is an ancient strategy in regulating NF-?B activation but also provides the first evidence, to our knowledge, for ABINs/A20-mediated inhibition of NF-?B via modifying the ubiquitinated proteins in a basal chordate, adding information on the stepwise development of vertebrate innate immune signaling.

SUBMITTER: Yuan S 

PROVIDER: S-EPMC4020044 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature