PMID- 26066081
OWN - NLM
STAT- MEDLINE
DCOM- 20160323
LR  - 20240210
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 6
DP  - 2015 Jun 12
TI  - WASH and Tsg101/ALIX-dependent diversion of stress-internalized EGFR from the 
      canonical endocytic pathway.
PG  - 7324
LID - 10.1038/ncomms8324 [doi]
LID - 7324
AB  - Stress exposure triggers ligand-independent EGF receptor (EGFR) endocytosis, but 
      its post-endocytic fate and role in regulating signalling are unclear. We show 
      that the p38 MAP kinase-dependent, EGFR tyrosine kinase (TK)-independent EGFR 
      internalization induced by ultraviolet light C (UVC) or the cancer therapeutic 
      cisplatin, is followed by diversion from the canonical endocytic pathway. Instead 
      of lysosomal degradation or plasma membrane recycling, EGFR accumulates in a 
      subset of LBPA-rich perinuclear multivesicular bodies (MVBs) distinct from those 
      carrying EGF-stimulated EGFR. Stress-internalized EGFR co-segregates with 
      exogenously expressed pre-melanosomal markers OA1 and fibrillar PMEL, following 
      early endosomal sorting by the actin polymerization-promoting WASH complex. 
      Stress-internalized EGFR is retained intracellularly by continued p38 activity in 
      a mechanism involving ubiquitin-independent, ESCRT/ALIX-dependent incorporation 
      onto intraluminal vesicles (ILVs) of MVBs. In contrast to the 
      internalization-independent EGF-stimulated activation, UVC/cisplatin-triggered 
      EGFR activation depends on EGFR internalization and intracellular retention. EGFR 
      signalling from this MVB subpopulation delays apoptosis and might contribute to 
      chemoresistance.
FAU - Tomas, Alejandra
AU  - Tomas A
AD  - Department of Cell Biology, UCL Institute of Ophthalmology, University College 
      London, 11-43 Bath Street, London EC1V 9EL, UK.
FAU - Vaughan, Simon O
AU  - Vaughan SO
AD  - Department of Cell Biology, UCL Institute of Ophthalmology, University College 
      London, 11-43 Bath Street, London EC1V 9EL, UK.
FAU - Burgoyne, Thomas
AU  - Burgoyne T
AD  - Department of Cell Biology, UCL Institute of Ophthalmology, University College 
      London, 11-43 Bath Street, London EC1V 9EL, UK.
FAU - Sorkin, Alexander
AU  - Sorkin A
AD  - Department of Cell Biology, University of Pittsburgh School of Medicine, 
      Pittsburgh, Pennsylvania 15261, USA.
FAU - Hartley, John A
AU  - Hartley JA
AD  - Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, 
      Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E 
      6BT, UK.
FAU - Hochhauser, Daniel
AU  - Hochhauser D
AD  - Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, 
      Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E 
      6BT, UK.
FAU - Futter, Clare E
AU  - Futter CE
AD  - Department of Cell Biology, UCL Institute of Ophthalmology, University College 
      London, 11-43 Bath Street, London EC1V 9EL, UK.
LA  - eng
GR  - 16569/CRUK_/Cancer Research UK/United Kingdom
GR  - R01 CA089151/CA/NCI NIH HHS/United States
GR  - C2559/A9994/CRUK_/Cancer Research UK/United Kingdom
GR  - CA089151/CA/NCI NIH HHS/United States
GR  - G1001684/MRC_/Medical Research Council/United Kingdom
GR  - 093445/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150612
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tsg101 protein)
RN  - 0 (WASH protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
CIN - Cell Cycle. 2015;14(21):3343-4. PMID: 26418166
MH  - DNA-Binding Proteins/*metabolism
MH  - *Endocytosis
MH  - Endosomal Sorting Complexes Required for Transport/*metabolism
MH  - ErbB Receptors/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Microfilament Proteins/*metabolism
MH  - Oxidative Stress
MH  - Protein Transport
MH  - Signal Transduction
MH  - Transcription Factors/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC4490399
EDAT- 2015/06/13 06:00
MHDA- 2016/03/24 06:00
PMCR- 2015/07/03
CRDT- 2015/06/13 06:00
PHST- 2014/10/09 00:00 [received]
PHST- 2015/04/27 00:00 [accepted]
PHST- 2015/06/13 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
PHST- 2015/07/03 00:00 [pmc-release]
AID - ncomms8324 [pii]
AID - 10.1038/ncomms8324 [doi]
PST - epublish
SO  - Nat Commun. 2015 Jun 12;6:7324. doi: 10.1038/ncomms8324.