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.
Rivera
José
J
Centro Nacional de Investigaciones Cardiovasculares Carlos III, E-28029 Madrid, Spain. jrivera@cnic.es
Megías
Diego
D
Bravo
Jerónimo
J
D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques
C410024:BRMS1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C431150:SNX6 protein, human; D058305:Sorting Nexins; D005982:Glutathione Transferase