title: Reprieval from execution: the molecular basis of caspase inhibition.
abstract: The suppression of apoptosis is essential to the propagation of viruses, and to the control of development and homeostasis in insects and mammals. The central components of all apoptotic pathways are proteases of the caspase family. Therefore, it is not surprising that the processes of natural selection, as well as pharmaceutical chemists, have designed compounds that directly target caspase activity in attempts to regulate apoptosis. The mechanisms used by highly specialized naturally occurring caspase inhibitors (both host and viral) have remained obscure for some time. However, recently there has been significant progress in this field, particularly because of the structural elucidation of the complexes between caspases and an endogenous inhibitor (XIAP) and a viral inhibitor (p35). This article reviews the newly defined molecular basis for the regulation of the caspases by viral and endogenous inhibitors.
authors.affiliation: The Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
authors.forename: Henning R
authors.initials: HR
authors.lastname: Stennicke
authors.forename: Ciara A
authors.initials: CA
authors.lastname: Ryan
authors.forename: Guy S
authors.initials: GS
authors.lastname: Salvesen
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D017924:Nucleopolyhedroviruses / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000502:physiology; D015398:Signal Transduction; D014764:Viral Proteins / Q000737:chemistry / Q000494:pharmacology; D051636:X-Linked Inhibitor of Apoptosis Protein
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D011506:Proteins; D015843:Serpins; D014764:Viral Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C081618:p35 protein, Nucleopolyhedrovirus; C074641:interleukin-1beta-converting enzyme inhibitor; D020169:Caspases