The Biological Function Of FAM122A Gene In Vivo And The Study Of Pml Interacting With LC3

Protein phosphatase 2A(PP2A)is an important member of serine and threonine protein phosphatase family and participates in a variety of biological processes including embryonic development,cell proliferation,apoptosis and signal transduction.A series of endogenous PP2 A inhibitors(ANP32a,SET,CIP2 A,ARPP16,ARPP19,TIP and TIPRL1)have essential roles in cancer occurrence and development.However,only limited investigation has been conducted on the potential roles of these PP2 A inhibitors in embryonic development process.Our previous work showed that FAM122A(family with sequence similarity 122A),is a newly identified endogenous PP2 A inhibitor.We used CRISPR/Cas9 technology to generate FAM122 A gene knockout C57BL/6 mice.Based on the analysis of genotyping in the offspring from intercrossing heterozygous FAM122 A deletion mice and phenotype observation,we found homozygous deletion in mice results in embryonic lethality at E10.5.Further,heterozygous FAM122 A deletion MEFs displayed the reduced growth with enhanced PP2 A activity.Therefore,FAM122 A is the first identified endogenous PP2 A inhibitor participating in embryonic development process.On the other hand,we previously reported that PML overexpression sequestrates part of microtubule-associated protein light chain 3(LC3)proteins in PML nuclear bodies.However,the potential biological significance of LC3 located in the nucleus is not clear.In this study,we found PML interacts with LC3 as determined by immune coprecipitation and immunofluorescence.In addition,the co-localization of PML with LC3 is significantly enhanced through PML overexpression induced by interferon ?.Furthermore,PML interacts with LC3 through two potential LC3 interaction regions(LIR)while thisinteraction does not depend on autophagy activity.In conclusion,we first demonstrated that PML interacts with LC3,which has an important role in the cell growth inhibition function of PML.