AI Article Synopsis

  • Local hyperthermia at 44°C can effectively treat HPV-infected skin lesions, but about 30% of patients don’t respond well, prompting research into improving this treatment.
  • To explore molecular targets for enhancing antiviral immunity, researchers performed a lysine succinylome assay on HaCaT cells exposed to different temperatures, validating their findings through various biochemical techniques.
  • The study identified 119 proteins with increased succinylation at higher temperatures, highlighting annexin A2 as a potential new drug target, which combined with local hyperthermia may lead to better treatment outcomes for warts.

Article Abstract

Background And Objectives: Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min).

Methods: The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein-protein interaction (PPI) was performed.

Results: A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2.

Conclusions: Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444469PMC
http://dx.doi.org/10.2478/jtim-2022-0061DOI Listing

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