Transcription and Growth Regulatory Functions of the HIN-200 Family of Proteins

Interferons have been shown to exert antiviral, cell growth regulatory, and immunomodulatory effects on target cells (16, 37). Both type I (α and β) and type II (γ) interferons regulate cellular activities by specifically inducing the expression or activation of endogenous proteins that perform distinct biological functions. The HIN-200 (hematopoietic interferon-inducible nuclear proteins with a 200-amino-acid repeat) gene family found on human and mouse chromosome 1 is positively regulated by type I and II interferons (15, 27, 30). The HIN-200 family of proteins consists of a number of highly homologous human and murine proteins with similar primary amino acid sequences and biological characteristics. The human HIN-200 family members include IFI 16 (39), the myeloid nuclear differentiation antigen (MNDA) (2, 18), and AIM-2 (absent in melanoma) (17), while the mouse HIN-200 family members include p202 (3), p203 (20), p204 (3), and D3 (38). There are a number of reviews that elegantly outline the biochemical characteristics of these proteins and their patterns of expression (15, 27, 30). Recently, there have been a number of reports examining possible cellular functions of HIN-200 proteins. It is now clear that these proteins play a role in modulating cell growth and perhaps in vivo differentiation, and the newest member of the HIN-200 family, AIM-2, has been identified as a possible tumor suppressor protein. Some family members are transcriptional regulators, acting either directly by binding DNA at a promoter or indirectly by modulating the function of other cellular transcription factors. Clearly, there is much still to learn about the biological functions of these proteins and how significant a role they play during an interferon response. While it is clear that the human and mouse family members share many biochemical and structural characteristics, it is unclear which, if any, of the currently identified murine HIN-200 proteins are functional homologs of the different human HIN-200 family members. This review will briefly cover the structural and biochemical properties of HIN-200 proteins but will concentrate on the molecular and biological functions of these molecules.