Grass carp (Ctenopharyngodon idella) Kat5 mediates P53 acetylation to induce apoptosis and promotes GCRV replication.

Abstract

Lysine acetyltransferase 5 (Kat5) is a member of the histone acetyltransferase family. In addition to modifying histones, Kat5 also acetylates non-histone proteins, thereby regulating their activity, stability, and localization. However, the roles of Kat5 remain largely unknown in lower vertebrates, particularly in teleosts. Here, our study identified an ortholog of Kat5 in Ctenopharyngodon idella (CiKat5). Notably, CiKat5 was induced by poly (I:C), GCRV and SVCV. Overexpression of Cikat5 led to the increase of several apoptosis-related genes, including bax, caspase3 and caspase9, whereasits knockdown downregulated these genes. Moreover, overexpression of Cikat5 can induce CIK cells apoptosis. Further assays revealed that CiKat5 interacted with P53, and this interaction was attributed to the acetyltransferase (MYST) domain of CiKat5 and the DNA-binding domain of P53. Mechanistic studies demonstrated that CiKat5 promoted P53 acetylation via its MYST domain, thereby cooperatively inducing apoptosis. In addition, CiKat5 suppressed Ifn i expression and enhanced the replication of GCRV. Thus, our study not only demonstrated that CiKat5 promoted P53-mediated apoptosis by acetylation but also indicated that CiKat5 is required for GCRV replication by suppressing Ifn i response. This research provides the novel insights into the role of fish Kat5 in apoptotic and immune signaling pathways.