6533b7d9fe1ef96bd126b8b8

RESEARCH PRODUCT

High frequency of a non-functional TAP1/LMP2 promoter polymorphism in human tumors

subject

description

The Tap1 and Tap2 genes encoding for a heterodimeric peptide transporter play a key role in antigen processing and presentation. The TAP complex mediates the transport of peptides generated by the IFN-gamma-inducible proteasome subunits LMP2, 7 and 10 from the cytosol into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. In contrast to the frequent polymorphisms within the rat Tap genes which exert functional differences, polymorphic regions within the human Tap genes have been demonstrated, but not systematically analyzed in terms of their functional significance. Both the Tap1 and Lmp2 genes are transcribed from a bidirectional intergenic promoter which is regulated by at least three sequences located in the Tap1 proximal region. We describe here a polymorphic site in the shared TAP1/LMP2 promoter which frequently occurred in human tumor cells of distinct origin. This polymorphism resulted in a Gright curved arrow T substitution 151 bp upstream of the translation start of Tap1. Using transient transfection assays with luciferase reporter constructs, the transcriptional activities of the different allelic variants of the TAP1/LMP2 promoter were comparable suggesting no functional consequences of this TAP1/LMP2 promoter polymorphism.