PCNA negatively regulates MITA through the autophagy pathway in miiuy croaker (Miichthys miiuy).

Interferon-mediated innate immune response is the first line of defense against foreign pathogen infection. Overexpression of MITA can activate the expression of interferon and promote the innate immune response of the body to the virus. These innate immune responses are tightly controlled to prevent the host from over-immunizing itself. In this study, we reported that structurally highly conserved PCNA negatively regulates MITA. PCNA overexpression can promote MITA degradation and block the expression of interferon, while the autophagy inhibitor 3-MA significantly inhibits MITA degradation, indicating that PCNA can degrade MITA through the autophagy pathway. PCNA inhibits interferon production by targeting MITA and avoids excessive immune response. In summary, our results indicate that PCNA is involved in the immune response by degrading MITA through the autophagy pathway, which will provide new ideas for further studies on the regulatory mechanism of immune signaling pathways in lower vertebrates.