Selective inhibition of calcineurin-NFAT signaling by blocking protein–protein interaction with small organic molecules
AUTOR(ES)
Roehrl, Michael H. A.
FONTE
National Academy of Sciences
RESUMO
Transient or reversible protein–protein interactions are commonly used to ensure efficient targeting of signaling enzymes to their cellular substrates. These interactions include direct binding to substrate, interaction with an accessory or scaffold protein, and positioning at subcellular locations in proximity to substrates. The existence of specialized targeting mechanisms raises the possibility of designing inhibitors that do not block enzyme activity per se, but rather interfere with targeting of the enzyme to one or more of its substrates within the cell. Here, we identify small organic molecules that specifically block targeting of the protein phosphatase calcineurin to its substrate nuclear factor of activated T cells (NFAT, also termed NFATc) and show that they are effective inhibitors of calcineurin-NFAT signaling.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=419644Documentos Relacionados
- Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes
- Spatial and temporal regulation of coronary vessel formation by calcineurin-NFAT signaling
- Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling
- c-Jun N-terminal kinases (JNK) antagonize cardiac growth through cross-talk with calcineurin–NFAT signaling
- Binding of small molecules to an adaptive protein–protein interface