Altered Lysine Crotonylation Identified in Psoriatic Skin
Lysine crotonylation, a post-translational modification previously studied in oncology, may play a role in psoriasis pathogenesis, according to a translational study comparing protein modification profiles in lesional and non-lesional skin. The findings introduce a potential epigenetic mechanism underlying disease activity in psoriasis.
Investigators analyzed skin samples from 45 patients with psoriasis, evaluating differences in lysine crotonylation between affected and unaffected tissue. While many crotonylation patterns were shared across both tissue types, distinct differences were observed in psoriatic lesions. A total of 100 crotonylation sites were upregulated and 76 were downregulated in lesional skin.
The most significantly upregulated modification was identified in COL6A3, while the most downregulated site was found in S100A9, a protein previously implicated in inflammatory pathways. These findings suggest that crotonylation may influence both structural and inflammatory components of psoriatic disease.
Bioinformatic analyses revealed enrichment of crotonylated proteins within the ribosome pathway in lesional skin, indicating a possible link between protein synthesis regulation and disease activity. The authors noted that these patterns may reflect broader alterations in cellular function within psoriatic lesions.
The study provides early evidence that “lysine crotonylation…has recently emerged as a prominent focus in post-translational modification research,” and that its dysregulation may be relevant beyond oncology. The authors concluded that their findings “offer preliminary evidence of altered lysine crotonylation in psoriatic skin and suggest its potential involvement in psoriasis pathogenesis.”
Further studies are needed to validate these findings and determine whether modulation of crotonylation pathways can influence disease activity or treatment response in psoriasis.
Reference
Dong P, Hao C, Li H, et al. Proteome analysis of lysine crotonylation modification in patients with psoriasis. PeerJ. 2026;14:e20922. Published online March 13, 2026. doi:10.7717/peerj.20922
