Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis

The EMBO Journal
Philbert LeeXiaoyang Wu

Abstract

Tissue homeostasis of skin is sustained by epidermal progenitor cells localized within the basal layer of the skin epithelium. Post-translational modification of the proteome, such as protein phosphorylation, plays a fundamental role in the regulation of stemness and differentiation of somatic stem cells. However, it remains unclear how phosphoproteomic changes occur and contribute to epidermal differentiation. In this study, we survey the epidermal cell differentiation in a systematic manner by combining quantitative phosphoproteomics with mammalian kinome cDNA library screen. This approach identified a key signaling event, phosphorylation of a desmosome component, PKP1 (plakophilin-1) by RIPK4 (receptor-interacting serine-threonine kinase 4) during epidermal differentiation. With genome-editing and mouse genetics approach, we show that loss of function of either Pkp1 or Ripk4 impairs skin differentiation and enhances epidermal carcinogenesis in vivo Phosphorylation of PKP1's N-terminal domain by RIPK4 is essential for their role in epidermal differentiation. Taken together, our study presents a global view of phosphoproteomic changes that occur during epidermal differentiation, and identifies RIPK-PKP1 signaling as novel axis...Continue Reading

References

Jul 1, 1983·The Journal of Investigative Dermatology·M PruniérasD Woodley
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·K J Green, C A Gaudry
Aug 27, 2002·Current Biology : CB·Pamela HollandJacques Peschon
Feb 28, 2003·Methods : a Companion to Methods in Enzymology·Shao-En OngMatthias Mann
Dec 17, 2003·The Journal of Biological Chemistry·Xiaoyang WuJun-Lin Guan
Apr 9, 2004·Nature Reviews. Molecular Cell Biology·Spiro GetsiosKathleen J Green
Apr 12, 2005·European Journal of Cell Biology·Ansgar Schmidt, Stephanie Jäger
Jul 11, 2006·Annual Review of Cell and Developmental Biology·Cédric Blanpain, Elaine Fuchs
Sep 15, 2007·Biochimica Et Biophysica Acta·David Garrod, Martyn Chidgey
Nov 15, 2007·Cell Cycle·Thomas A Khavari, John Rinn
Jan 23, 2008·The Journal of Cell Biology·Elaine Fuchs
Feb 4, 2009·The Journal of Cell Biology·Casey A Ydenberg, Mark D Rose
Jul 9, 2010·The Journal of Investigative Dermatology·Tammy Sobolik-DelmaireJames K Wahl
Nov 18, 2010·British Journal of Cancer·F KernM Baccarini
Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Markus Schober, Elaine Fuchs
Jun 28, 2011·Nature Methods·Xiaoping YangDavid E Root
Jul 30, 2011·Science·Nicolas StranskyJennifer R Grandis
Aug 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Elisabetta BottiAntonio Costanzo
Oct 11, 2011·Molecular Cell·Douglas R GreenGuy S Salvesen
Dec 16, 2011·Genes, Chromosomes & Cancer·Andrew M KazWilliam M Grady
Dec 27, 2011·American Journal of Human Genetics·Karen MitchellMichael J Dixon
Dec 27, 2011·American Journal of Human Genetics·Ersan KalayNurten A Akarsu
Oct 13, 2012·Biochemical and Biophysical Research Communications·Edmond H Fischer
Mar 26, 2013·The Journal of Clinical Investigation·Robert M HarmonKathleen J Green
Jul 31, 2013·Trends in Cell Biology·Oxana Nekrasova, Kathleen J Green
Dec 4, 2013·Cold Spring Harbor Perspectives in Medicine·Craig Nowell, Freddy Radtke
Feb 5, 2014·Cold Spring Harbor Perspectives in Medicine·Carolina N PerdigotoElena Ezhkova
Apr 18, 2014·Cell Communication & Adhesion·Daniela NitoiuDavid P Kelsell
Feb 20, 2015·Cell and Tissue Research·Joshua A BroussardKathleen J Green
Mar 19, 2015·Cellular Signalling·Mei Qi KwaGlen M Scholz

❮ Previous
Next ❯

Citations

Feb 13, 2018·Cellular and Molecular Life Sciences : CMLS·Giel TangheWim Declercq
Jul 26, 2018·Experimental Dermatology·Hyun Cheol BaeSang Wook Son
Sep 13, 2018·Expert Review of Proteomics·Maura Brioschi, Cristina Banfi
Apr 6, 2019·Cellular and Molecular Life Sciences : CMLS·Michael FuchsFranziska Vielmuth
Dec 12, 2019·Cell Biology International·Tuba DinçerErsan Kalay
Jun 20, 2020·Expert Review of Proteomics·Jörn DengjelAlexander Nyström
Jul 18, 2020·Journal of Clinical Medicine·Andreea D LazarMarieta Costache
Aug 1, 2020·Seminars in Cell & Developmental Biology·Gregory D Cuny, Alexei Degterev
Jan 22, 2020·Trends in Cell Biology·Tom DelangheMathieu J M Bertrand
Mar 14, 2021·American Journal of Medical Genetics. Part a·Tuba DinçerErsan Kalay
Jun 1, 2021·Biochemical and Biophysical Research Communications·Ji Yeon HongPierre D McCrea
Apr 5, 2019·Experimental and Molecular Pathology·Daniela HaaseYuan Chen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.