RNA Editing Cofactor-A1CF Competitive Binding To P65 Interaction Site On NKRF Induced Decreasing Of P65(Ser536) Phosphorylation And IFN-? Expression In Renal Carcinoma Cells

A1CF acts as an RNA-binding cofactor in APOBEC1-mediated C-to-U change in the edited transcript,physical interaction with APOBEC1 or RNA has been elaborated clearly,but its outside roles of RNA editing have not been addressed.Here,we demonstrate that A1 CF interacts with NKRF independent of RNA and DNA without affecting its expression and nuclear translocation,but modulates p65(Ser536)phosphorylation and IFN-? levels.Further truncation of A1 CF or deletion on NKRF reveals RRM1 domain of A1 CF and p65 binding motif on NKRF are necessary for their interaction,deletion of RRM1 on A1 CF abrogates NKRF binding and the decrease of IFN-? expression and p65(Ser536)phosphorylation induced by A1 CF.Moreover,full length of A1 CF,but not RRM1 deletion mutant,promotes cell proliferation in renal carcinoma cells.Perturbation of A1 CF levels in renal carcinoma cells alters anchorage-independent growth and tumor progression in nude mice,and p65(Ser536)phosphorylation and IFN-? expression are lower,but ki67 is much higher in A1 CF overexpressed-tumor tissues of xenograft mice model.Notably,primary and metastatic samples from renal cancer patients display high A1 CF expression,low p65(Ser536)phosphorylation and IFN-? levels in renal carcinoma tissues compared with corresponding paracancerous tissues.Our findings indicated that A1 CFdecreased p65 Ser536 phosphorylation and IFN-? levels maybe caused by A1 CF competitive binding to the p65-combined site on NKRF,and revealed the direct binding function of A1 CF independent of RNA or DNA in signal pathway regulation,and its tumor promotion characteristic in renal carcinoma cells.