Zinc Finger, MYM-Type Protein 4 (ZMYM4)

Domain analysis revealed that only full-length CDIR, and not its isolated 3-prime or 5-prime ends or ORF, confers resistance to cell killing. Mutation analysis revealed that the U-rich motifs AUUUUC and UUUCAUUUU are required for this protection. Resistance to cell killing was accompanied by elevated levels of p21 (CDKN1A) and BCL2 mRNA and protein. In vitro RNA-protein binding assays and Western blot analysis revealed that HSP27 (HSPB1) and all isoforms of AUF1 (HNRNPD) are components of a protein complex that binds CDIR. Use of recombinant proteins revealed that AUF1, but not HSP27, directly bound CDIR. Transfection of HeLa cells with another AUF1 target, the 3-prime UTR of MYC, also inhibited interferon-gamma-induced cell killing, but in a limited manner.