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The role of sentrin-specific protease 2 substrate recognition in TGF-β-induced tumorigenesis
- Source :
- Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018), Scientific Reports
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-β signals into the nuclei. Although many cellular factors are involved in TGF-β induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-β. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-β repression. The SENP2363~400 segment is critical for TGF-β-induced cell migration, which is correlated with SENP2363~400 deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-β induced cancer cell migration.
- Subjects :
- 0301 basic medicine
Cellular pathology
Carcinogenesis
SUMO protein
lcsh:Medicine
Matrix metalloproteinase
medicine.disease_cause
Article
Substrate Specificity
03 medical and health sciences
Cell Movement
Transforming Growth Factor beta
Spheroids, Cellular
medicine
Humans
Author Correction
lcsh:Science
Psychological repression
Smad4 Protein
Multidisciplinary
biology
Chemistry
lcsh:R
Sumoylation
Cell migration
Transforming growth factor beta
Cell biology
Cysteine Endopeptidases
030104 developmental biology
biology.protein
lcsh:Q
Transforming growth factor
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....3ba48b1c1e8adcab2ccca769c7b9e8e9