The Metastasis Suppressor Candidate Nucleotide Diphosphate Kinase NM23 Specifically Interacts with Members of the ROR/RZR Nuclear Orphan Receptor Subfamily

We have cloned proteins that interact with the nuclear orphan receptor RZRβ using the yeast two-hybrid system. We identified, amongst a number of other genes, the nucleoside diphosphate kinase (NDPK)-2 also known as Nm23-2, c-mycregulatory factor PuF and differentiation inhibitory factor. RZRβ specifically interacts with Nm23-2 but not with the closely related tumor metastasis suppressor candidate gene product Nm23-1. In contrast, RORα interacts with both Nm23 proteins. These findings were corroborated byin vitrointeraction assays based on GST-pulldown experiments. With n-mycwe propose a candidate gene regulated by RORα/RZRβ and Nm23, based on the finding that the respective DNA binding sites in the first intron are conserved in several mammalian species.