Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies

The mouse int-6 gene was identified in mammary tumors as an integration site for the mouse mammary tumor virus. Its human counterpart encodes a product that interacts with the Tax viral oncoprotein of the human T cell leukaemia virus type 1. This interaction impedes the localisation of over-expressed Int-6 in nuclear bodies containing the promyelocytic leukaemia gene product (PML). In this study, Int-6 is characterised as a 52 kDa protein that is localised within nuclear bodies in primary lymphocytes. Screening of a human B cell cDNA library for proteins that interact with Int-6 led to isolation of four clones coding for the p110 subunit of eIF3, in accordance with previous detection of Int-6 in purified forms of this translation initiation factor. Another clone was interesting with respect to the subcellular localisation of Int-6. It encodes the Ret finger protein (Rfp) which interacts with PML and localises within a subset of PML nuclear bodies. The interaction of Rfp with Int-6 is mediated through a region in Rfp designated 'Rfp domain', distinct from that involved in the interaction with PML. Int-6 and Rfp are co-localised in certain PML nuclear bodies in lymphocytes and transfection studies in HeLa cells strongly suggest that Rfp triggers translocation of Int-6 to nuclear bodies.