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

Abstract

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.

Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression

“…More generally, the regulation of gene expression by ligandregulated IR nuclear translocation is reminiscent of nuclear hormone receptors, which are ligand-regulated transcription factors (Cheung and Kraus, 2010), and signaling molecules such as Notch and b-catenin, which respond to extracellular signals by translocating from the plasma membrane to the nucleus to regulate transcription (Willert and Jones, 2006). Over the last decades, a number of RTKs that bind ligands at the cell surface have been found in the nucleus (Carpenter and Liao, 2013;Song et al, 2013;Mikula et al, 2016;Papadopoulos et al, 2018). By identifying a mechanism for insulin-regulated IR interaction with transcriptional machinery at key regulatory elements genome-wide, targeting a set of genes with a clear relationship to distinctive functions of the receptor, our results provide clear validation for a general principle where RTKs translocate to the nucleus and widely regulate gene expression.…”

Uptake and Fate of Extracellular Membrane Vesicles: Nucleoplasmic Reticulum-Associated Late Endosomes as a New Gate to Intercellular Communication

“…In addition to EV cargo, this pathway might play a role in the nuclear translocation of plasma membrane receptors upon ligand interaction. Similar to integral membrane proteins CD9 and CD133 [ 5 , 52 , 233 , 234 , 235 ], numerous plasma membrane receptors including EGFR, platelet-derived growth factor (PDGF), insulin growth factor receptor 1 (IGF-1R), and several G-protein coupled receptors that are potential drug targets were surprisingly found in the nuclear compartment [ 236 , 237 , 238 , 239 ]. Therein, they could be involved in transcriptional regulation and cellular proliferation, and confer chemo- and radio-resistance among other biochemical processes.…”

The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors

“…In addition, the proposed involvement of the COPI coat argued in favor of trafficking through the Golgi [49]. The involvement of the Golgi apparatus is also proposed for the PDGFR-b receptor trafficking to the nucleus [7]. These authors further suggested the involvement of the TATA element–modifying factor 1 (TMF-1), which has been shown to be involved in the Rab6-dependent trafficking from the Golgi to the ER [50].…”

“…Similarly, various groups have used Brefeldin A, a potent inhibitor of GTP exchange factors for the Arfs small GTPAses and a drug inducing full disassembly of the Golgi [55]. Subcellular fractionation experiments in different studies have indicated that treating cells with BFA results in a decrease in the nuclear levels of EGFR and PDGFR [7,49]. By contrast, we did not find that the number of NAEs per cell is significantly affected after treatment with BFA, not did it affect EGFR traffic to the nucleus [13].…”

“…Yet, the nuclear localization concerns a great number of receptor tyrosine kinases (RTKs) with essential biological functions, such as the EGFR, its paralog ERB2, the fibroblast growth factor receptor 1 (FGFR-1), the vascular endothelial growth factor receptor 1 (VEGFR1) and the platelet derived growth factor receptor beta (PGDFR-b) [1,5,6,7]. Nuclear EGFR was shown to be full length, excluding the hypothesis of cleavage-mediated release from membranes.…”