Differential occurrence of lysine 2-hydroxyisobutyrylation in psoriasis skin lesions

Abstract Lysine2-hydroxyisobutyrylation is a newly discovered posttranslational modification. Although this modification is an important type of protein acylation, its role in psoriasisremains unstudied. We compared lesional and nonlesional psoriasisskin samples from 45 psoriasispatients. The result showed that this highly conserved modification was found in large quantities in both normal and diseased dermal tissues. However, there were a number of clear and significant differences between normal and diseased skin tissue. By comparing, lysine2-hydroxyisobutyrylation was upregulated at 94 sites in 72 proteins and downregulated at 51 sites in 44 proteins in lesional skin. In particular, the sites with the most significant downregulation of lysine2-hydroxyisobutyrylation were found in S100A9(ratio = 0.140, p -value = .000371), while the most upregulated site was found in tenascin(ratio = 3.082, p-value = .0307). Loci associated with psoriasis, including FUBP1, SERPINB2 and S100A9, also exhibited significant regulation. Analyses of proteome data revealed that SERPINB2 and S100A9were differentially expressed proteins. And bioinformatics analysis suggest that the P13K-Akt signaling pathway was more enriched with lysine2-hydroxyisobutyrylation in lesional psoriasisskin. Our study revealed that lysine2-hydroxyisobutyrylation is broadly present in psoriasisskin, suggesting that this modification plays a role in psoriasispathogenesis. Significance A newly discovered protein posttranslational modification, lysine2-hydroxyisobutyrylation, has been found to occur in a wide variety of organisms and to participate in some important metabolic processes. In this study, lysine2-hydroxyisobutyrylation in lesional psoriasisskin and nonlesional psoriasisskin was quantified and compared for the first time. We found a number of differentially modified proteins and sites in our comparisons. Interestingly, some of the identified proteins and pathways with significantly different modifications, such as S100A9and the PI3K-Akt signaling pathway, have been previously reported to be associated with psoriasis. We hope that this research will provide new insights into psoriasis.