Abstract
HIN‐200 proteins are interferon‐inducible proteins capable of regulating cell growth, senescence, differentiation and death. Using a combination of in silico analysis of NCBI EST databases and screening of murine C57BL/6 cDNA libraries we isolated novel murine HIN‐200 cDNAs designated Ifi206~S~ and Ifi206~L~ encoding two putative mRNA splice variants. The p206~S~ and p206~L~ protein isoforms have a modular domain structure consisting of an N‐terminal PAAD/DAPIN/Pyrin domain, a region rich in serine, threonine and proline residues and a C‐terminal 200 B domain characteristic of other HIN‐200 proteins. Ifi206 mRNA was detected only in the spleen and lung of BALB/c and C57BL/6 mice and expression was up‐regulated by both types I and II IFN subtypes. p206 protein was predominantly expressed in the cytoplasm and addition of LMB, a CRM1 dependent nuclear export inhibitor, caused p206 to accumulate in the nucleus. Unlike other human and mouse HIN‐200 proteins that contain only a single 200 amino acid domain, overexpression of p206 impaired the clonogenic growth of tumour cell lines. Thus, p206 represents the newest HIN‐200 family member discovered. It has distinct and restricted pattern of expression however maintains many of the hallmarks of HIN‐200 proteins including the presence of a characteristic 200 X domain, induction by interferon and an ability to suppress tumour cell growth. J. Cell. Biochem. 103: 1270–1282, 2008. © 2007 Wiley‐Liss, Inc.