Molecular cloning and characterization of a human homologue of TBPIP, a BRCA1 locus-related gene.

ABSTRACT

Here we clone the human homologue of TBPIP [Tat binding protein 1(TBP-1)-interacting protein]. TBPIP is a molecule that has been cloned from mouse as a cofactor of TBP-1. Eighty-eight per cent of the deduced amino acid sequence of human TBPIP coincides with that of mouse TBPIP. CAT assay reveals that human TBPIP could interact with human TBP-1, then enhance the function of TBP-1 on HIV (human immunodeficiency virus)-Tat-mediated transactivation. Our radiation hybrid mapping indicates that TBPIP is located on chromosome 17q12-21. A DNA database search uncovers that an apparent part of TBPIP has been obtained as a BRCA1 locus-related gene (OV-4) and mapped onto chromosome 17q12-21. Interestingly, the nucleotide structure of human TBPIP is very similar to that of the GT198 gene, which has been cloned from a human breast cancer cell line and also mapped onto the BRCA1 locus. Since a very high rate of gene mutation is observed in the BRCA1-related region in breast cancers and expression of authentic GT198 mRNA could not be confirmed in either BT-474 (other kind of human breast cancer cell line) or normal human testis (where the strong expression of GT198 mRNA is reported), it is likely that GT198 is a mutated form of human TBPIP.