Histone deacetylase 10 (HDAC10) is implicated in pathological conditions such as cancer and inflammatory diseases. While histone deacetylases (HDACs) primarily regulate gene expression via histone deacetylation, their roles in modifying non-histone substrates, particularly transcription factors, are increasingly recognized as important for disease mechanisms. Although HDAC10 is known to deacetylate nuclear substrates in disease-relevant pathways, its specific non-histone targets remain largely unexplored. Given that the transcription factor activator protein-1 (AP-1)/c-Jun centrally regulates genes involved in matrix metalloproteinases, inflammation, and oncogenic programs, HDAC10-dependent regulation of c-Jun activity may provide a mechanistic link between HDAC10 and these disease processes. This study identifies c-Jun as a nuclear substrate of HDAC10 and characterizes the effects of HDAC10-mediated deacetylation on AP-1 activity. In human embryonic kidney 293 cells, HDAC10 interacts with both wild-type c-Jun and a δ-domain deletion mutant (Δδ c-Jun), reduces their lysine acetylation, and suppresses c-Jun- and Δδ c-Jun-driven AP-1 luciferase activity. HDAC10 also decreases c-Jun DNA-binding activity, indicating that deacetylation limits its transcriptional activity. Collectively, overall these results suggest that HDAC10 negatively regulates AP-1-dependent transcription by deacetylating c-Jun independently of the δ-domain, and further support the hypothesis that HDAC10–c-Jun signaling contributes to the role of HDAC10 in cancer and inflammatory disease.

Abstract
INTRODUCTION
MATERIALS AND METHODS
    Cell culture and transfection
    Plasmids
    Co‑immunoprecipitation and immunoblotting
    Analysis of c‑Jun acetylation
    Activator protein-1 luciferase reporter assay
    c‑Jun DNA‑binding enzyme-linked immunosorbent assay
    Statistical analysis
RESULTS
    Histone deacetylase 10 interacts with c‑Jun
    Histone deacetylase 10 deacetylates c‑Jun and Δδ c‑Jun
    Histone deacetylase 10 suppresses activator protein-1 transcriptional activity drivenby c‑Jun and Δδ c‑Jun
    Histone deacetylase 10 inhibits c‑Jun DNA‑binding activity
DISCUSSION
REFERENCES

• So-Hyun Park(College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Sang-Myeong Lee(College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea) Corresponding author