Chronic Cigarette Smoke Exposure Subdues PP2A Activity by Enhancing Expression of the Oncogene CIP2A.

American Journal of Respiratory Cell and Molecular Biology
Sridesh NathPatrick Geraghty

Abstract

Phosphatase activity of the major serine threonine phosphatase, protein phosphatase 2A (PP2A), is blunted in the airways of individuals with chronic obstructive pulmonary disease (COPD), which results in heightened inflammation and proteolytic responses. The objective of this study was to investigate how PP2A activity is modulated in COPD airways. PP2A activity and endogenous inhibitors of PP2A were investigated in animal and cell models of COPD. In primary human bronchial epithelial (HBE) cells isolated from smokers and donors with COPD, we observed enhanced expression of cancerous inhibitor of PP2A (CIP2A), an oncoprotein encoded by the KIAA1524 gene, compared with cells from nonsmokers. CIP2A expression was induced by chronic cigarette smoke exposure in mice that coincided with a reduction in PP2A activity, airspace enlargements, and loss of lung function, as determined by PP2A phosphatase activity, mean linear intercept analysis, and forced expiratory volume in 0.05 second/forced vital capacity. Modulating CIP2A expression in HBE cells by silencing RNA or chemically with erlotinib enhanced PP2A activity, reduced extracellular-signal-regulated kinase phosphorylation, and reduced the responses of matrix metalloproteinases 1 a...Continue Reading

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Citations

Nov 2, 2019·American Journal of Respiratory Cell and Molecular Biology·Sridesh NathPatrick Geraghty
Nov 2, 2019·American Journal of Respiratory Cell and Molecular Biology·Ion CristóbalJesús García-Foncillas
Jan 15, 2019·American Journal of Respiratory and Critical Care Medicine·Declan F DohertyPatrick Geraghty
Apr 9, 2019·American Journal of Respiratory and Critical Care Medicine·Wassim W LabakiSurya P Bhatt
Aug 16, 2018·American Journal of Respiratory Cell and Molecular Biology·Xiuying Li, Toru Nyunoya
Feb 26, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Hui WeiRong Liu
Feb 21, 2019·American Journal of Respiratory and Critical Care Medicine·Srikanth R Janga, Sarah F Hamm-Alvarez

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BETA
transgenic

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