PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element–modifying factor 1
| Autor: | Johan Lennartsson, Carl-Henrik Heldin, Natalia Papadopoulos |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male 0301 basic medicine Becaplermin Golgi Apparatus Ligands Article Receptor tyrosine kinase Chromatin remodeling Receptor Platelet-Derived Growth Factor beta 03 medical and health sciences Cell Line Tumor medicine Humans Biotinylation Nuclear Matrix Receptor Research Articles Cell Proliferation Cell Nucleus biology Cell Biology Protein-Tyrosine Kinases Chromatin Assembly and Disassembly Nuclear matrix Chromatin Cell biology DNA-Binding Proteins Protein Transport Cell nucleus 030104 developmental biology medicine.anatomical_structure biology.protein Tyrosine kinase Platelet-derived growth factor receptor Protein Binding Signal Transduction Transcription Factors |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | PDGFRβ translocates to the nucleus in a ligand-dependent manner tethered by TATA element–modifying factor 1 (TMF-1). Papadopoulos et al. show that PDGFRβ interacts with TMF-1 and Fer kinase in the nucleus, regulating chromatin remodeling by the SWI–SNF complex and controlling proliferation via a p21-dependent mechanism. Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB–induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells. In the nucleus, PDGFRβ formed ligand-inducible complexes with the tyrosine kinase Fer and its substrate, TATA element–modifying factor 1 (TMF-1). PDGF-BB stimulation decreased TMF-1 binding to the transcriptional regulator Brahma-related gene 1 (Brg-1) and released Brg-1 from the SWI–SNF chromatin remodeling complex. Moreover, knockdown of TMF-1 by small interfering RNA decreased nuclear translocation of PDGFRβ and caused significant up-regulation of the Brg-1/p53-regulated cell cycle inhibitor CDKN1A (encoding p21) without affecting PDGFRβ-inducible immediate-early genes. In conclusion, nuclear interactions of PDGFRβ control proliferation by chromatin remodeling and regulation of p21 levels. |
| Databáze: | OpenAIRE |
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