Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunosuppressants cyclosporin and FK506 block the calcium-dependent signal-transduction pathway emanating from the T-cell receptor, thereby inhibiting the activation of helper T cells. Using these drugs as probes, chemists and biologists have uncovered several intracellular signaling molecules bridging the generation of second-messenger Ca2+ ion and the transcriptional activation of IL-2, among which are calmodulin, calcineurin and the nuclear factor of activated T cells (NF-AT). Hence, Ca2+ binds to calmodulin, leading to the binding of calmodulin to calcineurin; the activated calcineurin, in turn, may dephosphorylate the cytoplasmic subunit of NF-AT, resulting in its translocation from the cytoplasm into the nucleus to form a competent transcriptional activator. As described by Jun Liu these drugs manifest their effects in an unprecedented fashion. They do not directly intercept intracellular signaling molecules. Instead, they form tight complexes with two different classes of abundant cytosolic receptors called immunophilins upon entering the cell, and consequently inhibit their peptidyl prolyl cis-trans isomerase activities. The two structurally distinct immunophilin-drug complexes bind to, and inhibit, the phosphatase activity of calcineurin.
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PMID:FK506 and cyclosporin, molecular probes for studying intracellular signal transduction. 769 Oct 65

The immunosuppressants ciclosporin and FK506 block the Ca(2+)-dependent signal-transduction pathway emanating from the T-cell receptor, thereby inhibiting the activation of helper T cells. Using these drugs as probes, chemists and biologists have uncovered several intracellular signalling molecules bridging the generation of second-messenger Ca2+ ions and the transcriptional activation of IL-2, among which are calmodulin, calcineurin and the nuclear factor of activated T cells (NF-AT). Hence, Ca2+ binds to calmodulin, leading to the binding of calmodulin to calcineurin; the activated calcineurin, in turn, may dephosphorylate the cytoplasmic subunit of NF-AT, resulting in its translocation from the cytoplasm into the nucleus to form a competent transcriptional activator. As described by Jun Liu, these drugs manifest their effects in an unprecedented fashion. They do not directly intercept intracellular signalling molecules. Instead, they form tight complexes with two different classes of abundant cytosolic receptors called immunophilins upon entering the cell, and consequently inhibit their peptidyl prolyl cis-trans isomerase activities. The two structurally distinct immunophilin-drug complexes bind to, and inhibit, the phosphatase activity of calcineurin.
 ...
PMID:FK506 and ciclosporin: molecular probes for studying intracellular signal transduction. 769 52