The tumor suppressor p53 abrogates Smad-dependent collagen gene induction in mesenchymal cells.

The Journal of Biological Chemistry
Asish K GhoshJohn Varga

Abstract

The pleiotropic cytokine transforming growth factor-beta (TGF-beta) is a potent inducer of collagen synthesis and is implicated in the pathogenesis of fibrosis. Acting in concert with transcriptional coactivators p300/CBP, the Smads mediate TGF-beta stimulation of collagen synthesis in human dermal fibroblasts. Little information exists regarding positive and negative modulation of physiological TGF-beta responses. Because the tumor suppressor p53 is implicated in connective tissue homeostasis, here we examined the regulation of collagen gene expression by p53. Forced expression of ectopic p53 in dermal fibroblasts repressed basal and TGF-beta-stimulated collagen gene expression, whereas the absence of cellular p53 was associated with significantly enhanced transcriptional activity of the Type I collagen gene (COL1A2) and collagen synthesis. Ectopic expression of p53 also repressed TGF-beta stimulation of promoter activity driven by minimal Smad-binding elements, suggesting that p53 modulated Smad-dependent intracellular signaling. Inhibition was not due to altered levels, phosphorylation, or nuclear translocation of cellular Smads. Treatment of fibroblasts with etoposide, a potent inducer of cellular p53, abrogated TGF-beta st...Continue Reading

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Citations

Jan 21, 2010·Clinical Reviews in Allergy & Immunology·Matthias Geyer, Ulf Müller-Ladner
Apr 28, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Asish K GhoshJohn Varga
Jun 15, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Peedikayil E ThomasBethany B Moore
Mar 3, 2007·The Journal of Clinical Investigation·John Varga, David Abraham
Feb 23, 2008·The Journal of Clinical Investigation·Hong-Liang LiPeter P Liu
Apr 18, 2009·Reproductive Sciences·Kathleen A ConnellHugh S Taylor
Mar 12, 2005·Current Rheumatology Reports·Hironobu Ihn
Mar 11, 2008·Rheumatic Diseases Clinics of North America·John A Varga, Maria Trojanowska
Jul 13, 2007·Journal of Dermatological Science·Praveen R AranyAnita B Roberts
Apr 16, 2014·Journal of Cellular Biochemistry·Asish K Ghosh
Apr 21, 2012·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·A KulićM Sirotković-Skerlev
Jan 20, 2007·Biochemical and Biophysical Research Communications·Asish K GhoshJohn Varga
Apr 26, 2016·Nature Reviews. Nephrology·Xiao-Ming MengHui Yao Lan
Nov 25, 2016·Journal of Cellular Physiology·Asish K GhoshDouglas E Vaughan
Apr 6, 2011·Journal of Cellular Physiology·Asish K Ghosh, Douglas E Vaughan
Nov 21, 2015·Circulation·Varun NagpalDouglas E Vaughan
Jun 15, 2007·Journal of Cellular Physiology·Asish K Ghosh, John Varga
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Apr 28, 2018·International Journal of Molecular Sciences·Laia CajaIsabel Fabregat
Feb 20, 2016·Oncotarget·Carlos J Rodríguez-HernándezCarmen de Torres
Jul 19, 2019·Experimental and Therapeutic Medicine·Maimaiti YisireyiliKelimu Abudureyimu
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natalia NacuSergei P Atamas
Jul 17, 2013·Experimental Biology and Medicine·Asish K GhoshDouglas E Vaughan
May 10, 2019·International Journal of Cosmetic Science·M Perez-AsoB Martínez-Teipel
Aug 12, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David MarsolaisJérôme Frenette

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