Kindlin-1 protects cells from oxidative damage through activation of ERK signalling

Free Radical Biology & Medicine
Hila EmmertValerie G Brunton

Abstract

Kindlin-1 is a FERM domain containing adaptor protein that is found predominantly at cell-extracellular matrix adhesions where it binds to β-integrin subunits and is required for integrin activation. Loss of function mutations in the FERMT1 gene which encodes Kindlin-1 leads to the development of Kindler Syndrome (KS) an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, and predisposition to aggressive squamous cell carcinoma (SCC). Here we show that loss of Kindlin-1 sensitizes both SCC cells and keratinocytes to oxidative stress: Kindlin-1 deficient cells have higher levels of reactive oxygen species, decreased viability and increased DNA damage after treatment with either hydrogen peroxide (H2O2) or irradiation with UVA. We show that Kindlin-1 is required to fully activate ERK signalling after oxidative damage, and that activation of ERK protects cells from DNA damage following oxidative stress: inhibition of ERK activation sensitizes Kindlin-1 expressing cells, but not Kindlin-1 deficient cells to oxidative stress. Finally we demonstrate that the Kindlin-1 dependent activation of ERK and protection from DNA damage following oxidative stress depends on the ability of Kindlin-1 to bind inte...Continue Reading

References

Jan 1, 1985·American Journal of Medical Genetics·S Hacham-Zadeh, A A Garfunkel
Jan 1, 1994·International Journal of Radiation Biology·P A Riley
Nov 23, 2000·Nature·T Finkel, N J Holbrook
Jul 13, 2002·Journal of Cellular Physiology·Jennifer L Martindale, Nikki J Holbrook
Oct 4, 2002·Nutrition·Yun-Zhong FangGuoyao Wu
Mar 22, 2003·Current Opinion in Cell Biology·Toren Finkel
Apr 13, 2004·Oncogene·Teiji Wada, Josef M Penninger
Jun 10, 2004·Microbiology and Molecular Biology Reviews : MMBR·Philippe P Roux, John Blenis
Jun 13, 2006·Cardiovascular Research·Miklós Geiszt
Nov 7, 2006·Skinmed·Patrick O EmanuelRobert G Phelps
Nov 17, 2006·The Journal of Investigative Dermatology·David R Bickers, Mohammad Athar
Jan 24, 2007·Physiological Reviews·Karen Bedard, Karl-Heinz Krause
Jun 5, 2008·Antioxidants & Redox Signaling·Dunyaporn TrachoothamPeng Huang
Jul 26, 2008·The British Journal of Dermatology·C HasL Bruckner-Tuderman
Jan 6, 2009·The British Journal of Dermatology·J E Lai-CheongJ A McGrath
Jan 6, 2009·Skin Pharmacology and Physiology·L ZastrowL Ferrero
Feb 24, 2009·Nature·Peter J CookMichael G Rosenfeld
Mar 26, 2009·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·L ZastrowL Ferrero
Apr 8, 2010·Free Radical Research·Geou-Yarh Liou, Peter Storz
Mar 5, 2011·Microbiology and Molecular Biology Reviews : MMBR·Marie Cargnello, Philippe P Roux
Aug 13, 2011·Journal of the National Cancer Institute·Soraya SinKeltouma Driouch
Nov 30, 2011·Seminars in Cutaneous Medicine and Surgery·Holly E Kanavy, Meg R Gerstenblith
Jan 31, 2012·Cellular Signalling·Paul D RayYoshiaki Tsuji
May 9, 2012·Nature Cell Biology·Ralph Thomas BöttcherReinhard Fässler
May 15, 2012·Seminars in Cell & Developmental Biology·Cassandra L BuchheitZachary T Schafer
Jun 28, 2013·Nature Communications·Hitesh PatelValerie G Brunton
Jul 9, 2013·Biochimica Et Biophysica Acta·Paolo PaoliPaola Chiarugi
Dec 19, 2013·Genes & Cancer·Hari K KoulSweaty Koul
Apr 1, 2014·Nature Medicine·Emanuel RognoniReinhard Fässler
Sep 23, 2014·Biological Reviews of the Cambridge Philosophical Society·Anna StinconeMarkus Ralser
Sep 30, 2014·Cellular & Molecular Immunology·Arvind PandaySanjay Batra
Dec 22, 2014·Orphanet Journal of Rare Diseases·Elisabeth Zapatero-SolanaMarcela Del Rio
Jan 6, 2016·Journal of Cell Science·Emanuel RognoniReinhard Fässler
Mar 20, 2016·Journal of Molecular Cell Biology·Hitesh PatelValerie G Brunton
Oct 25, 2016·The Journal of Investigative Dermatology·Gaofeng ZhangBing Song
Nov 1, 2016·Human Molecular Genetics·Kristin MaierCristina Has

❮ Previous
Next ❯

Citations

Jul 1, 2018·American Journal of Clinical Dermatology·Amanda F NahhasHenry W Lim
Sep 27, 2018·Journal of Cellular and Molecular Medicine·Meijuan ZhouHaibo Wang
Nov 20, 2019·International Journal of Molecular Sciences·Angelo Giuseppe CondorelliDaniele Castiglia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Related Papers

The Journal of Investigative Dermatology
Gaofeng ZhangBing Song
Acta Dermato-venereologica
Tanasit TechanukulJoey E Lai-Cheong
Cancer Biology & Therapy
Elizabeth K Duperret, Todd W Ridky
© 2022 Meta ULC. All rights reserved