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PMID:20830743

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Citation

Rivera, J, Megías, D and Bravo, J (2010) Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression. J. Cell. Biochem. 111:1464-72

Abstract

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.

Links

PubMed Online version:10.1002/jcb.22874

Keywords

Cell Line; Fluorescence Resonance Energy Transfer; Glutathione Transferase/genetics; Glutathione Transferase/metabolism; HeLa Cells; Humans; Microscopy, Confocal; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Protein Binding; Sorting Nexins/genetics; Sorting Nexins/metabolism; Transcription, Genetic/genetics; Transcription, Genetic/physiology; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BRMS1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRMS1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRMS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UNH7

F

Seeded From UniProt

complete

HUMAN:SNX6

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SNX6

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9HCU9

F

Seeded From UniProt

complete

HUMAN:BRMS1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRMS1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRMS1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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