These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: REGγ is critical for skin carcinogenesis by modulating the Wnt/β-catenin pathway.
    Author: Li L, Dang Y, Zhang J, Yan W, Zhai W, Chen H, Li K, Tong L, Gao X, Amjad A, Ji L, Jing T, Jiang Z, Shi K, Yao L, Song D, Liu T, Yang X, Yang C, Cai X, Xu W, Huang Q, He J, Liu J, Chen T, Moses RE, Fu J, Xiao J, Li X.
    Journal: Nat Commun; 2015 Apr 24; 6():6875. PubMed ID: 25908095.
    Abstract:
    Here we report that mice deficient for the proteasome activator, REGγ, exhibit a marked resistance to TPA (12-O-tetradecanoyl-phorbol-13-acetate)-induced keratinocyte proliferation, epidermal hyperplasia and onset of papillomas compared with wild-type counterparts. Interestingly, a massive increase of REGγ in skin tissues or cells resulting from TPA induces activation of p38 mitogen-activated protein kinase (MAPK/p38). Blocking p38 MAPK activation prevents REGγ elevation in HaCaT cells with TPA treatment. AP-1, the downstream effector of MAPK/p38, directly binds to the REGγ promoter and activates its transcription in response to TPA stimulation. Furthermore, we find that REGγ activates Wnt/β-catenin signalling by degrading GSK-3β in vitro and in cells, increasing levels of CyclinD1 and c-Myc, the downstream targets of β-catenin. Conversely, MAPK/p38 inactivation or REGγ deletion prevents the increase of cyclinD1 and c-Myc by TPA. This study demonstrates that REGγ acts in skin tumorigenesis mediating MAPK/p38 activation of the Wnt/β-catenin pathway.
    [Abstract] [Full Text] [Related] [New Search]