Recently published as an open access Mini Review in The FEBS Journal* Sandra Peiró, Principal Investigator of VHIO’s Chromatin Dynamics in Cancer Group, and Gemma Serra-Bardenys, a Post-Doctoral Fellow of Sandra’s team, have co-authored a comprehensive review on enzymatic lysine oxidation as a posttranslational modifier of the macromolecular makeup of proteins and subsequent regulator of their function, stability and/or localization, as well as protein-protein and/or protein-nucleic acid interactions.
The oxidative reactions involving lysine residues that are regulated by the lysyl oxidase (LOX) family of proteins have long since been described, and the implication of these proteins in biological processes has been the focus of a significant body of research over the past few decades.
Mounting evidence now shows that lysine-derived oxidation is more abundant than previously thought. It is actually a regulator of many other proteins above and beyond the originally described extracellular substrates. Strikingly, LOX enzymes have now been shown to posttranslationally modify various proteins, including intracellular and even nuclear ones.
“In this review, we sought to highlight the new substrates and functions of oxidation which remain unresolved or are less commonly studied, including the oxidation of histones and transcription factors,” observed Sandra Peiró, Corresponding Author of this present review. She continued, “In particular, we discuss the latest insights into these recently described substrates and the role of LOX enzymes as posttranslational modulators of proteins in crucial biological processes including development, differentiation, proliferation, and cancer.”
LOX-mediated oxidation: cause and effect
Providing an in-depth review of several new substrates and functions of oxidation by the LOX family of proteins, the authors highlight the causal factors, biological interactions and effects in each case. They then go on to discuss the oxidation of nonhistone proteins and present a list of confirmed LOX- and LOXL-oxidizes substrates. Drawing on findings recently reported by other groups, they highlight the particularities, implications and biological effects of LOX activity in each case.
“While several structural and functional features of lysyl oxidase proteins are now well described, much research is still required in order to fully decipher the implications of these enzymes,” said Gemma Serra-Bardenys, co-author of this review article.
She added, “We therefore briefly discussed the current methods of identifying these oxidize proteins, and highlighted the pros and cons of each approach. Moving forward, novel and repurposed techniques will further facilitate the detection of posttranslational modification and thus respond to the many questions that remain without resolve.”
Fittingly, the authors conclude with a proposed checklist of open questions that will need to be addressed in order to reveal deeper insights into posttranslational modification as a regulator of protein function.
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Reference:
* Serra-Bardenys G, Peiró S. Enzymatic lysine oxidation as a posttranslational modification. FEBS J. 2021 Sep 18. doi: 10.1111/febs.16205. Epub ahead of print. PMID: 34535954.
