Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16

Interferons are important in regulating cell growth and differentiation, im mune function and initiating anti-viral responses. While the pleotrophic ac tions of interferons have been well documented, the molecular mechanisms un derpinning their biological effects have not been fully characterized. IFI 16 is a member of the interferon-inducible HIN-200 family of nuclear protei ns, which we have recently shown can function as a potent transcriptional r epressor. A murine member of the HIN-200 family, p202, can indirectly inter act with p53 via the p53 binding protein (p53bp) and inhibit p53-mediated t ranscriptional activation. The binding activity of p202 to p53bp was shown to require the conserved MFHATVAT motif present in all 200 amino acid repea t regions of HIN-200 proteins. Given that IFI 16 contains two MFHATVAT moti fs, we sought to determine whether IFI 16 may form a complex with p53 and i f so to ascertain the functional significance of this interaction. We demon strate that IFI 16 can directly bind to the C-terminal region of p53 and au gment p53-mediated transcriptional activation without altering the steady s tate levels of p53. Thus, in addition to its ability to directly regulate g ene expression, IFI 16 can also modulate the transcription function of othe r cellular transcription factors. These findings demonstrate a possible lin k between gene induction following interferon stimulation and p53-mediated cellular events.