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

• Publication year

  2018

• Venue

  Journal of Cell Biology

• Publication date

  2018-05-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.201706118PMID 29545370PMCID 5940298
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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