Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China; Key Laboratory of Major Autoimmune Diseases, Hefei, China.
Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China; Key Laboratory of Major Autoimmune Diseases, Hefei, China; The Comprehensive Lab, College of Basic medicine, Anhui Medical University, China.
J Proteomics. 2019 Aug 15;205:103420. doi: 10.1016/j.jprot.2019.103420. Epub 2019 Jun 20.
Lysine 2-hydroxyisobutyrylation is a newly discovered posttranslational modification. Although this modification is an important type of protein acylation, its role in psoriasis remains unstudied. We compared lesional and nonlesional psoriasis skin samples from 45 psoriasis patients. 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, lysine 2-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 lysine 2-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 S100A9 were differentially expressed proteins. And bioinformatics analysis suggest that the P13K-Akt signaling pathway was more enriched with lysine 2-hydroxyisobutyrylation in lesional psoriasis skin. Our study revealed that lysine 2-hydroxyisobutyrylation is broadly present in psoriasis skin, suggesting that this modification plays a role in psoriasis pathogenesis. SIGNIFICANCE: A newly discovered protein posttranslational modification, lysine 2-hydroxyisobutyrylation, has been found to occur in a wide variety of organisms and to participate in some important metabolic processes. In this study, lysine 2-hydroxyisobutyrylation in lesional psoriasis skin and nonlesional psoriasis skin 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 S100A9 and 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.
赖氨酸 2-羟异丁酰化是一种新发现的翻译后修饰。虽然这种修饰是蛋白质酰化的重要类型之一，但它在银屑病中的作用仍未被研究。我们比较了 45 名银屑病患者的皮损和非皮损皮肤样本。结果表明，这种高度保守的修饰在正常和患病的真皮组织中都大量存在。然而，正常和患病皮肤组织之间存在许多明显的差异。通过比较，在皮损皮肤中，赖氨酸 2-羟异丁酰化在 72 种蛋白质的 94 个位点上调，在 44 种蛋白质的 51 个位点下调。特别是，赖氨酸 2-羟异丁酰化下调最明显的位点是 S100A9（比值=0.140，p 值=0.000371），而上调最明显的位点是 tenascin（比值=3.082，p 值=0.0307）。与银屑病相关的基因座，包括 FUBP1、SERPINB2 和 S100A9，也表现出明显的调节。蛋白质组数据分析表明，SERPINB2 和 S100A9 是差异表达蛋白。生物信息学分析表明，PI3K-Akt 信号通路在皮损银屑病皮肤中富含赖氨酸 2-羟异丁酰化。我们的研究表明，赖氨酸 2-羟异丁酰化广泛存在于银屑病皮肤中，提示该修饰在银屑病发病机制中发挥作用。意义：一种新发现的蛋白质翻译后修饰，赖氨酸 2-羟异丁酰化，已在多种生物体中发现，并参与一些重要的代谢过程。在这项研究中，我们首次定量比较了皮损和非皮损银屑病皮肤中的赖氨酸 2-羟异丁酰化。我们在比较中发现了一些差异修饰的蛋白质和位点。有趣的是，一些鉴定出的具有显著差异修饰的蛋白质和途径，如 S100A9 和 PI3K-Akt 信号通路，先前已被报道与银屑病有关。我们希望这项研究能为银屑病提供新的见解。
