Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat shock factor 1 (HSF1) is the master transcriptional regulator of chaperone genes. HSF1 regulates the expression of the immediate-early response gene IER5, which encodes a protein that has roles in the stress response and cell proliferation. Here, we have shown that IER5 interacts with protein phosphatase 2A (PP2A) and its B55 regulatory subunits. Expression of IER5 and B55 in cells leads to HSF1 dephosphorylation and activation of HSF1 target genes. The B55 subunits directly bind to HSF1. These results suggest that IER5 functions as a positive feedback regulator of HSF1 and that this process involves PP2A/B55 and HSF1 dephosphorylation.
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PMID:HSF1 transcriptional activity is modulated by IER5 and PP2A/B55. 2581 51

Cyclin-dependent kinase (CDK)-activating phosphatases, CDC25A and CDC25B, are labile proteins, and their levels vary in a cell cycle-dependent manner. Immediate-early response IER5 protein negatively regulates the cellular CDC25B levels, and stress-induced IER5 expression potentiates G2/M arrest. IER5 binds to protein phosphatase PP2A and regulates the PP2A substrate specificity. We show that IER5 binds to CDC25B and assists PP2A to convert CDC25B to hypophosphorylated forms. Hypophosphorylation at Ser323 results in the dissociation of CDC25B from 14-3-3 phospho-binding proteins. In IER5 expressing cells, CDC25B dissociated from 14-3-3 is unstable but slightly activated, because 14-3-3 inhibits CDC25B polyubiquitination and CDC25B binding to CDK1. The 14-3-3 binding to CDC25A also impedes CDC25A degradation and CDC25A-CDK2 interaction. We propose that 14-3-3 is an important regulator of CDC25A and CDC25B and that PP2A/IER5 controls the stability and activity of CDC25B through regulating the interaction of CDC25B and 14-3-3.
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PMID:Regulation of the stability and activity of CDC25A and CDC25B by protein phosphatase PP2A and 14-3-3 binding. 3046 67

Proteins encoded by immediate-early response (IER) family genes, IER2, IER5, and IER5L, share homology at their N-terminal regions. IER5 binds to protein phosphatase 2A (PP2A) and enhances dephosphorylation of PP2A target proteins such as heat shock factor HSF1. Here, we show the expression of IER family genes and the target protein-specific function of IER proteins. The IER homology regions of IER2 and IER5L are required for the interaction with PP2A. Expression of IER2 and IER5L in cells leads to reduced phosphorylation of HSF1 and derepression of its transcriptional activity. Although IER5 and IER5L enhance dephosphorylation of ribosomal protein S6 kinase, IER2 fails to do so. IER2, IER5, and IER5L all bind to the cell cycle regulator CDC25A and convert it to the hypophosphorylated form, which causes dissociation from 14-3-3 regulatory protein. IER5 differentially regulates CDC25A levels in cells under normal and thermal stress conditions. These results suggest that IER proteins are target protein-specific regulators of PP2A activity and modulate cell proliferation through CDC25A activity.
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PMID:IER family proteins are regulators of protein phosphatase PP2A and modulate the phosphorylation status of CDC25A. 3059 13