Protein Post-Translational Modifications in UV-Induced Skin Damage

Ultraviolet (UV) irradiation leads to acute photodamage, photoaging and skin cancers. Post-translational modifications (PTMs) represent a key regulatory layer by modulating protein function, localization and interactions under UV stress. This review discusses the mechanistic involvement of PTMs in UV-induced skin damage and summarizes emerging PTM-related photoprotective strategies. Phosphorylation is a central mediator of UV-induced signal transduction, driving activation of the epidermal growth factor receptor (EGFR) and its downstream signalling pathways. Acetylation exerts distinct regulatory effects: histone acetylation primarily regulates transcription of inflammation-related genes and matrix metalloproteinases (MMPs), while non-histone acetylation modulates cellular senescence and mitochondrial antioxidant defence through modification of key proteins. Ubiquitination regulates protein degradation and, through non-degradative modifications, participates in DNA damage recognition and nucleotide excision repair (NER). Furthermore, other PTMs, including methylation, glycosylation, citrullination, SUMOylation and poly(ADP-ribosyl)ation (PARylation), participate in diverse regulatory processes during UV-induced cutaneous alterations. Experimental and emerging interventions associated with PTMs in UV-induced skin damage range from natural extracts to small-molecule agents and mainly include upstream-level modulation of oxidative stress, metabolic status or key effector protein function, as well as enzyme-level modulation of PTM writers and erasers. Different classes of PTMs contribute to UV-induced skin damage through distinct regulatory mechanisms. Further studies should explore the roles of emerging and less-characterized PTMs and evaluate interventions targeting PTM-regulating enzymes in physiologically relevant skin models.