TRIM5 alpha is a member of tripartite motif protein family and recently identified as a restriction factor for retroviral infection in a species-specific manner. Human TRIN15 alpha gene is located on chromosomal position 11p15 in a cluster with other TRIM genes including TRIM6, 21, 22, and 34. We show here that interferon (IFN) upregulates TRIM5 alpha mRNA expression in HeLa and HepG2 cells by performing Northern blot analysis and quantitative real-time PCR. TRIM5 alpha promoter activity was IFN inducible as confirmed by luciferase assay using a reporter plasmid that contained the 5 '-flanking region of TRIM5 alpha. Mutational analysis has revealed that IFNs activate TRIM5 alpha promoter activity through a putative in terferon- stimulated response element (ISRE). Intriguingly, another IFN-responsive protein signal transducer and activator of transcription factor I (STAT1) binds to the ISRE sequence as shown by electrophoretic mobility shift assay using HeLa cell extracts. We have raised a specific polyclonal antibody against TRIM5ot and confirmed that TRIM5ot protein expression is inducible by IFN-beta in HeLa cells. These results lead us to define that the transcription and protein synthesis of TRIM5 alpha could be modulated by IFN, suggesting that TRIM5 alpha may play a role in an IFN-induced antiviral state against retrovirus infection. (c) 2005 Elsevier Inc. All rights reserved.