Xin Zhao,Wenji Huang,Yanjie Shi,Jiahong Guo,Hehe Xiao,Ning Ji,Jianhua Feng,Huifeng Dang,Jun Zou
PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.
Xin Zhao,Wenji Huang,Jiahong Guo,Ning Ji,Jianhua Feng,Yanjie Shi,Kangyong Chen,Jun Zou
PLAAT1 belongs to the PLAAT family and plays regulatory roles in cell growth, tumor suppression and phospholipid metabolism . However, whether PLAAT1 is involved in p53 mediated signaling has not been investigated. Here, we report that PLAAT1 promotes degradation of p53 in zebrafish. We found that the plaat1 gene was constitutively expressed in tissues including liver, kidney , spleen , intestine, eye and brain , with relative higher expression levels detected in the brain and eye. Overexpression of plaat1 led to inhibition of p53 and tnfα mRNA expression. Furthermore, it was shown that PLAAT1 interacted with p53 to facilitate p53 degradation via autophagy-lysosome dependent pathway. Our work indicates that PLAAT1 is involved in the interplay between p53 mediated cellular responses and autophagy.