dc.contributor.author | Maruthappu, T | en_US |
dc.contributor.author | Chikh, A | en_US |
dc.contributor.author | Fell, B | en_US |
dc.contributor.author | Delaney, PJ | en_US |
dc.contributor.author | Brooke, MA | en_US |
dc.contributor.author | Levet, C | en_US |
dc.contributor.author | Moncada-Pazos, A | en_US |
dc.contributor.author | Ishida-Yamamoto, A | en_US |
dc.contributor.author | Blaydon, D | en_US |
dc.contributor.author | Waseem, A | en_US |
dc.contributor.author | Leigh, IM | en_US |
dc.contributor.author | Freeman, M | en_US |
dc.contributor.author | Kelsell, DP | en_US |
dc.date.accessioned | 2017-01-27T10:56:27Z | |
dc.date.available | 2016-12-06 | en_US |
dc.date.issued | 2017-01-27 | en_US |
dc.date.submitted | 2017-01-26T09:39:56.370Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/19007 | |
dc.description.abstract | Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated. | en_US |
dc.description.sponsorship | The study was
supported by grants awarded to D.P.K. from the Medical Research Council (MR/
L010402/1), Cancer Research UK (C7570/A19107), British Heart Foundation (RG/13/19/
30568), Nanodrug FP7-ITN and the 2016 CHANEL-CERIES research award. T.M. holds
an MRC Clinical Research Training fellowship (MR/K002740/1). M.F. holds grants
awarded by the Wellcome Trust (101035/Z/13/Z) and the Medical Research Council
(U105178780). A.M.-P. holds a fellowship from the Fundacio´n Alfonso Martı´n Escudero. | en_US |
dc.format.extent | 14174 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Animals | en_US |
dc.subject | Carrier Proteins | en_US |
dc.subject | Cell Line | en_US |
dc.subject | Cell Proliferation | en_US |
dc.subject | Cytoskeleton | en_US |
dc.subject | Down-Regulation | en_US |
dc.subject | Epidermal Cells | en_US |
dc.subject | Epidermis | en_US |
dc.subject | Esophageal Neoplasms | en_US |
dc.subject | Female | en_US |
dc.subject | Fibroblasts | en_US |
dc.subject | Gain of Function Mutation | en_US |
dc.subject | Humans | en_US |
dc.subject | Keratin-16 | en_US |
dc.subject | Keratin-6 | en_US |
dc.subject | Keratinocytes | en_US |
dc.subject | Keratoderma, Palmoplantar | en_US |
dc.subject | Male | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Knockout | en_US |
dc.subject | Pressure | en_US |
dc.subject | RNA, Small Interfering | en_US |
dc.subject | Stress, Physiological | en_US |
dc.subject | Tissue Culture Techniques | en_US |
dc.subject | Up-Regulation | en_US |
dc.subject | Wound Healing | en_US |
dc.title | Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s) 2017 | |
dc.identifier.doi | 10.1038/ncomms14174 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/28128203 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 8 | en_US |
dcterms.dateAccepted | 2016-12-06 | en_US |
qmul.funder | iRHOM/ADAM17 in oesophageal squamous cell cancer::Cancer Research UK | en_US |
qmul.funder | iRHOM/ADAM17 in oesophageal squamous cell cancer::Cancer Research UK | en_US |