PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element-modifying factor 1

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 beta (PDG FR beta) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDG FR beta was dependent on PDGF-BB-induced receptor dimerization, clathrin-mediated endocytosis, beta-importin, and intact Golgi, occurring in both normal and cancer cells. In the nucleus, PDG FR beta 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 PDG FR beta and caused significant up-regulation of the Brg-1/p53-regulated cell cycle inhibitor CDKN1A (encoding p21) without affecting PDG FR beta-inducible immediate-early genes. In conclusion, nuclear interactions of PDG FR beta control proliferation by chromatin remodeling and regulation of p21 levels.