Okadaic acid inhibits dephosphorylation of cytoplasmic p53 during lymphocyte activation.
A competition radioimmunoassay specific for conserved Domain V of p53 revealed that Domain V was masked in highly phosphorylated cytosolic p53 of resting T lymphocytes and unmasked through dephosphorylation during lymphocyte activation. Phosphatase type 2A was shown to act upon immunopurified p53 in a manner that increased the immunoreactivity of the molecule in the Domain V RIA. Treatments of T cells with okadaic acid (1nM) prior to addition of Concanavalin-A/serum inhibited completely the dephosphorylation of cytosolic p53 observed to occur within 10-20min of stimulation. Brief exposure of T cells to okadaic acid during the first hour of activation by mitogens produced increased rates of cellular proliferation. Sustained inhibition of the dephosphorylation of cytoplasmic p53 in cells undergoing mitogenic stimulation may affect adversely the ability of p53 to exert its anti-proliferative effect and could contribute to unregulated cell growth.
McClure
J E
JE
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Noonan
C A
CA
Shearer
W T
WT
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D002467:Cell Nucleus / Q000378:metabolism; D002846:Chromatography, Affinity; D003208:Concanavalin A; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011863:Radioimmunoassay; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000302:isolation & purification / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004988:Ethers, Cyclic; D010455:Peptides; D016159:Tumor Suppressor Protein p53; D003208:Concanavalin A; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases