Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression

Sorting nexin 6 (SNX6), a predominantly cytoplasmic protein involved in intracellular trafficking of membrane receptors, was identified as a TGF-β family interactor. However, apart from being a component of the Retromer, little is known about SNX6 cellular functions. Pim-1-dependent SNX6 nuclear translocation has been reported suggesting a putative nuclear role for SNX6. Here, we describe a previously non-reported association of SNX6 with breast Cancer metastasis suppressor 1 (BRMS1) protein detected by a yeast two-hybrid screening. The interaction can be reconstituted in vitro and further FRET analysis confirmed the novel interaction. Additionally, we identified their coiled-coil domains as the minimal binding motives required for interaction. Since BRMS1 has been shown to repress transcription, we sought the ability of SNX6 to interfere with this nuclear activity. Using a standard gene reporter assay, we observed that SNX6 increases BRMS1-dependent transcriptional repression. Moreover, over-expression of SNX6 was capable of diminishing trans-activation in a dose-dependent manner.