RESUMEN
Smad2 is a crucial component of intracellular signaling by transforming growth factor-ß (TGFß). Here we describe that Smad2 is glycosylated, which is a novel for Smad2 post-translational modification. We showed that the Smad2 glycosylation was inhibited upon treatment of cells with 17ß-estradiol, and was enhanced in cells in a dense culture as compared to cells in a sparse culture. The Smad2 glycosylation was not dependent on the C-terminal phosphorylation of Smad2, and was not affected by TGFß1 treatment of the cells. Smad2 was glycosylated at multiple sites, and one of the predicted sites is Serine110. Thus, Smad2 is glycosylated, and this post-translational modification was modulated by 17ß-estradiol but not by TGFß1.
Asunto(s)
Procesamiento Proteico-Postraduccional , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Alanina/genética , Animales , Células CHO , Recuento de Células , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Concanavalina A/farmacología , Cricetinae , Cricetulus , Estradiol/farmacología , Glicosilación , Humanos , Lectinas/farmacología , Células MCF-7 , Mutación/genética , Lectinas de Plantas/farmacología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Serina/genéticaRESUMEN
BACKGROUND/AIM: Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation. MATERIALS AND METHODS: Proteomics, immunohistochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells. RESULTS: We report here that invasiveness network highlighted the involvement of hallmarks such as cell proliferation, migration, cell death, genome stability, immune system regulation and metabolism. Identified involvement of cell-virus interaction and gene silencing are potentially novel cancer mechanisms. Identified 6,113 nodes with 11,055 edges affecting 1,085 biological processes show extensive re-arrangements in cell physiology. These high numbers are in line with a similar broadness of networks built with diagnostic signatures approved for clinical use. CONCLUSION: Our data emphasize a broad systemic regulation of invasiveness, and describe the network of this regulation.