Fig. 2

Regulation of FADD. FADD expression and activity are regulated by distinct mechanisms, including genetic and chromosomal alterations, DNA methylation, TFs, ncRNAs, and PTMs. (A-F) HIF-1α, allelic losses or chromosomal deletions, DNA amplification, BRCA1, gene mutations or polymorphisms and DNA methylation alter FADD expression and activity at the transcription level. (G) FIST/HIPK3, PLK1, and CKIα facilitate the translocation of FADD from the cytoplasm to the nucleus by mediating its phosphorylation at Ser194. (H) CK2 promote the nuclear localization by mediating its phosphorylation at Ser200. (I) AURA phosphorylates FADD at Ser203 in response to Taxol exposure. (J) LUBAC, MKRN1, and CHIP inhibit the formation of DISC by facilitating the degradation of FADD in an ubiquitin-proteasome dependent manner. (K) NleB1 promoted the GlcNAcylation of FADD at Arg117, thereby antagonizing the DR-induced apoptosis. (L) SUMOylation of FADD facilitates the recruitment of Drp1 onto the mitochondria by enhancing its binding to Drp1, resulting in mitochondrial-fragmentation-associated necrosis. (M) MiRNA promotes the degradation of FADD mRNA by directly targeting its 3′UTR. (N) H19 downregulates FADD by sponging miR-675. (O) Circ 001418 increased FADD levels by targeting miR-1297