Uev1A amino terminus stimulates poly-ubiquitin chain assembly and is required for NF- κB activation.

Uev1A amino terminus stimulates poly-ubiquitin chain assembly and is required for NF-κB activation.
Cell Signal. 2020 Jul 10;:109712
Authors: Wu Z, Andersen PL, Moraes T, McKenna SA, Zhang Y, Zhang W, Ellison MJ, Xiao W
Abstract
The ubiquitin (Ub)-conjugating enzyme variants (Uev) Uev1A and Mms2 interact with Ubc13 to form heterodimeric complexes with different biological functions. Uev1A-Ubc13 is involved in NF-κB activation while Mms2-Ubc13 is required for the DNA-damage response. The structural comparison of the core domains of these two Uevs reveals no obvious difference, suggesting that the amino terminal extension of Uev1A plays a critical role in the functional determination. Indeed, truncated Uev1A lacking the N-terminal extension behaves like Mms2, while a chimeric protein containing the N-terminal Uev1A fused to Mms2 functionally resembles Uev1A. Interestingly, the N-terminal extension of Uev1A also dictates whether to assemble di- or poly-Ub chains in an in vitro reaction. Both thermodynamic measurements and enzymatic assays revealed that the Uev1A N-terminal extension weakens the Uev-Ubc13 interaction; however, other means capable of causing a reduced Uev1A-Ubc13 affinity and poly-Ub chain assembly do not necessarily promote NF-κB activation, indicating that the poly-Ub chain formation is not the only component contributed by the N-terminal extension of Uev1A. The physiological relevance of the Uev1A N-terminal truncat...

Source: Cellular Signalling - July 9, 2020 Category: Cytology Authors: Wu Z, Andersen PL, Moraes T, McKenna SA, Zhang Y, Zhang W, Ellison MJ, Xiao W Tags: Cell Signal Source Type: research