Abstract
The Na,K-ATPase classically serves as an ion pump creating an electrochemical gradient across the plasma membrane that is essential for transepithelial transport, nutrient uptake and membrane potential. In addition, Na,K-ATPase also functions as a receptor, a signal transducer and a cell adhesion molecule. With such diverse roles, it is understandable that the Na,K-ATPase subunits, the catalytic α-subunit, the β-subunit and the FXYD proteins, are controlled extensively during development and to accommodate physiological needs. The spatial and temporal expression of Na,K-ATPase is partially regulated at the transcriptional level. Numerous transcription factors, hormones, growth factors, lipids, and extracellular stimuli modulate the transcription of the Na,K-ATPase subunits. Moreover, epigenetic mechanisms also contribute to the regulation of Na,K-ATPase expression. With the ever growing knowledge about diseases associated with the malfunction of Na,K-ATPase, this review aims at summarizing the best-characterized transcription regulators that modulate Na,K-ATPase subunit levels. As abnormal expression of Na,K-ATPase subunits has been observed in many carcinoma, we will also discuss transcription factors that are associated with epithelial-mesenchymal transition, a crucial step in the progression of many tumors to malignant disease.
Highlights
Na,K-ATPase is an integral membrane protein that mainly functions as an ion pump, hydrolyzing one molecule of ATP to pump three Na+ out of the cell in exchange for two K+ entering the cell per pump cycle
The expression of Na,K-ATPase is transcriptionally regulated by hormones, growth factors, lipid mediators and other extracellular stimuli through mediating transcription factor binding to promoter regions of Na,K-ATPase subunits
Various recently identified transcriptional regulators of Na,KATPase are transcription factors that are activated during development, in stem cells and during epithelial-mesenchymal transition (EMT)
Summary
Na,K-ATPase is an integral membrane protein that mainly functions as an ion pump, hydrolyzing one molecule of ATP to pump three Na+ out of the cell in exchange for two K+ entering the cell per pump cycle. Besides being an ion pump, Na,K-ATPase acts as a signal transducer (Xie and Askari, 2002; Pierre and Xie, 2006; Rajasekaran and Rajasekaran, 2009; Reinhard et al, 2013). Both αand β-subunit associate with various signaling molecules, including Src, phosphoinositide 3-kinase (PI3K), caveolin-1, protein phosphatase 2, and EGFR thereby activating a number of intracellular. Na,K-ATPase regulates the formation and stabilization of intercellular junctions and the β1 and β2-subunits act as cell adhesion molecules (Gloor et al, 1990; Rajasekaran et al, 2001a,b; Vagin et al, 2006, 2012)
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