PMID- 10213689 OWN - NLM STAT- MEDLINE DCOM- 19990511 LR - 20190619 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 284 IP - 5414 DP - 1999 Apr 23 TI - Fas-induced caspase denitrosylation. PG - 651-4 AB - Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways. FAU - Mannick, J B AU - Mannick JB AD - Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. joan_mannick@dfci.harvard.edu FAU - Hausladen, A AU - Hausladen A FAU - Liu, L AU - Liu L FAU - Hess, D T AU - Hess DT FAU - Zeng, M AU - Zeng M FAU - Miao, Q X AU - Miao QX FAU - Kane, L S AU - Kane LS FAU - Gow, A J AU - Gow AJ FAU - Stamler, J S AU - Stamler JS LA - eng GR - GM57601-01/GM/NIGMS NIH HHS/United States GR - HL52529/HL/NHLBI NIH HHS/United States GR - HL59130/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Enzyme Inhibitors) RN - 0 (Enzyme Precursors) RN - 0 (Nitrites) RN - 0 (Nitroso Compounds) RN - 0 (S-Nitrosothiols) RN - 0 (fas Receptor) RN - 27JT06E6GR (omega-N-Methylarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 60-24-2 (Mercaptoethanol) RN - 67616-44-8 (S-nitrosomercaptoethanol) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) RN - K848JZ4886 (Cysteine) SB - IM MH - Animals MH - Apoptosis MH - Binding Sites MH - Caspase 3 MH - Caspases/*metabolism MH - Cell Line MH - Cysteine/*metabolism MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Enzyme Precursors/metabolism MH - Humans MH - *Mercaptoethanol MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase/antagonists & inhibitors MH - Nitrites/metabolism MH - Nitroso Compounds/metabolism MH - *S-Nitrosothiols MH - Signal Transduction MH - fas Receptor/*physiology MH - omega-N-Methylarginine/pharmacology EDAT- 1999/04/24 00:00 MHDA- 1999/04/24 00:01 CRDT- 1999/04/24 00:00 PHST- 1999/04/24 00:00 [pubmed] PHST- 1999/04/24 00:01 [medline] PHST- 1999/04/24 00:00 [entrez] AID - 10.1126/science.284.5414.651 [doi] PST - ppublish SO - Science. 1999 Apr 23;284(5414):651-4. doi: 10.1126/science.284.5414.651.