Asparagine Hydroxylation is a Reversible Post-translational Modification

Abstract

Amino acid hydroxylation is a common post-translational modification, which generally regulates protein interactions or adds a functional group that can be further modified. Such hydroxylation is currently considered irreversible, necessitating the degradation and re-synthesis of the entire protein to reset the modification. Here we present evidence that the cellular machinery can reverse FIH-mediated asparagine hydroxylation on intact proteins. These data suggest that asparagine hydroxylation is a flexible and dynamic post-translational modification akin to modifications involved in regulating signaling networks, such as phosphorylation, methylation and ubiquitylation.

Keywords: Post-translational modifications; SILAC; affinity proteomics; factor-inhibiting-HIF; hydroxylation; mass spectrometry; signal transduction.