Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression.

Autor: Warner DR; University of Louisville Birth Defects Center, School of Dentistry, 501 South Preston Street, Louisville, KY 40202, United States., Smith SC; University of Louisville Birth Defects Center, School of Dentistry, 501 South Preston Street, Louisville, KY 40202, United States., Smolenkova IA; University of Louisville Birth Defects Center, School of Dentistry, 501 South Preston Street, Louisville, KY 40202, United States., Pisano MM; University of Louisville Birth Defects Center, School of Dentistry, 501 South Preston Street, Louisville, KY 40202, United States. Electronic address: drmikeky@gmail.com., Greene RM; University of Louisville Birth Defects Center, School of Dentistry, 501 South Preston Street, Louisville, KY 40202, United States.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2016 Mar 01; Vol. 342 (1), pp. 32-8. Date of Electronic Publication: 2016 Feb 24.
DOI: 10.1016/j.yexcr.2016.02.015
Abstrakt: p300 is a multifunctional transcriptional coactivator that interacts with numerous transcription factors and exhibits protein/histone acetyltransferase activity. Loss of p300 function in humans and in mice leads to craniofacial defects. In this study, we demonstrated that inhibition of p300 histone acetyltransferase activity with the compound, C646, altered the expression of several genes, including Cdh1 (E-cadherin) in mouse maxillary mesenchyme cells, which are the cells that give rise to the secondary palate. The increased expression of plasma membrane-bound E-cadherin was associated with reduced cytosolic β-catenin, that led to attenuated signaling through the canonical Wnt pathway. Furthermore, C646 reduced both cell proliferation and the migratory ability of these cells. These results suggest that p300 histone acetyltransferase activity is critical for Wnt-dependent palate mesenchymal cell proliferation and migration, both processes that play a significant role in morphogenesis of the palate.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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