The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR

Scharaw, Sandra; Iskar, Murat; Ori, Alessandro; Boncompain, Gaëlle; Laketa, Vibor; Poser, Ina; Lundberg, Emma; Perez, Franck; Beck, Martin; Bork, Peer; Pepperkok, Rainer

doi:10.1083/jcb.201601090

Cited by 47 publications

(77 citation statements)

References 64 publications

(88 reference statements)

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“…The minimal COPII machinery required to generate cargoladen, ER-derived transport carriers has been defined for several years, but regulators of this pathway continue to emerge, several of which are expressed only in metazoan organisms, which have evolved more complex systems to control cargo efflux in response to environmental and developmental cues (62,63). Biochemical and genetic screens in human cells, Drosophila, and C. elegans have identified several factors that play important roles at the ER in cargo selection, exit site organization, and modulating secretory capacity, but components that facilitate movement of COPII-coated carriers between the ER and ERGIC have been more challenging to define (55,(64)(65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER–Golgi intermediate compartments

Hanna

Block

Frankel

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The conserved coat protein complex II (COPII) mediates the initial steps of secretory protein trafficking by assembling onto subdomains of the endoplasmic reticulum (ER) in two layers to generate cargo-laden transport carriers that ultimately fuse with an adjacent ER–Golgi intermediate compartment (ERGIC). Here, we demonstrate that Trk-fused gene (TFG) binds directly to the inner layer of the COPII coat. Specifically, the TFG C terminus interacts with Sec23 through a shared interface with the outer COPII coat and the cargo receptor Tango1/cTAGE5. Our findings indicate that TFG binding to Sec23 outcompetes these other associations in a concentration-dependent manner and ultimately promotes outer coat dissociation. Additionally, we demonstrate that TFG tethers vesicles harboring the inner COPII coat, which contributes to their clustering between the ER and ERGIC in cells. Together, our studies define a mechanism by which COPII transport carriers are retained locally at the ER/ERGIC interface after outer coat disassembly, which is a prerequisite for fusion with ERGIC membranes.

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Section: Discussionmentioning

confidence: 99%

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER–Golgi intermediate compartments

Hanna

Block

Frankel

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…A novel regulatory mechanism occurring at the EEs has been recently described, which is able to sense the amount of EGFRs trafficking toward the endosomes and to induce de novo receptor biosynthesis and exocytosis, in order to preserve EGFR levels at the PM (Scharaw et al, 2016). When cells are continuously stimulated with high EGF doses, the transcription factor RNF11 translocates from the EEs to the nucleus where it induces transcription of genes required for EGFR transport to the PM (Scharaw et al, 2016). How RNF11 senses the amount of internalized EGFR at the EEs remains an open question.…”

Section: Temporal Regulation Of Egfr Signaling By Endocytosismentioning

confidence: 99%

Emerging functions of the EGFR in cancer

2017

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The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level. Despite the large body of knowledge obtained over the last two decades, previously unrecognized (herein defined as ‘noncanonical’) functions of the EGFR are currently emerging. Here, we will initially review the canonical ligand‐induced EGFR signaling pathway, with particular emphasis to its regulation by endocytosis and subversion in human tumors. We will then focus on the most recent advances in uncovering noncanonical EGFR functions in stress‐induced trafficking, autophagy, and energy metabolism, with a perspective on future therapeutic applications.

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“…According to this finding, it was suggested that Sec16 acts as a central node in a coherent feed‐forward loop (CFFL) which integrates growth factor signaling and ER export . More recently, it was shown that prolonged stimulation with epidermal growth factor (EGF) also induces the gene expression of several COPII components such as Sec23B, Sec24B, and Sec24D (Fig. ).…”

Section: Signaling To the Ermentioning

confidence: 98%

Crosstalk of endoplasmic reticulum exit sites and cellular signaling

Centonze

Farhan

2019

FEBS Letters

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The synthesis, quality control, and trafficking of a third of the eukaryotic proteome takes place at the endoplasmic reticulum (ER), which is the largest cellular organelle. Thus, biosynthetic trafficking from the ER, although constitutive, has to be tightly controlled. Increasing evidence indicates that the ER acts as a platform that initiates signaling events. In this review, we focus on signaling pathways that target components of the ER export machinery to regulate protein export. In addition, we discuss how signaling generated at the ER regulates various homeostatic cellular processes such as cell growth and proliferation, and how the deregulation thereof is involved in disease.

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The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR

Cited by 47 publications

References 64 publications

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER–Golgi intermediate compartments

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER–Golgi intermediate compartments

Emerging functions of the EGFR in cancer

Crosstalk of endoplasmic reticulum exit sites and cellular signaling

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