Landscape of ubiquitination events that occur in host skin in response to tick (Haemaphysalis longicornis) bitten.

Ticks are major parasites of domestic livestock, wildlife, and humans. After a tick bite, diverse cutaneous manifestations initially occur in the bitten area in the host. In this study, a label-free proteomics approach was applied to identify the differentially ubiquitinated proteins (DUPs) induced by tick-bitten in the skin. In total, 113 proteins were ubiquitinated in rabbit skin during tick bitten period, among which the ubiquitination levels of 43 proteins were altered. These DUPs in skin subjected to tick-bitten were enriched in metabolic processes, immune processes, and protein degradation processes. Bioinformatic analysis suggested that tick bitten may regulate the glycolysis pathway in host skin via differential ubiquitination of GAPDH, HK1 and TPI1, while regulate the ubiquitin-proteasome system, the MHC-I and MHC-II antigen-presenting pathways, and the HIF-1 signaling pathway via differential ubiquitination of MEK1, PSMC3, PSMA6, MHC-II and PSMD1. Moreover, PSMC3, PSMA6, PSMD1 and MEK1 were demonstrated as novel targets of ubiquitination. This study provides the first overview of ubiquitination in host skin affected by tick bitten and broadens our knowledge of the molecular mechanism involved in tick bitten.