Reprieval from execution: the molecular basis of caspase inhibition.
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.
Stennicke
Henning R
HR
The Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Ryan
Ciara A
CA
Salvesen
Guy S
GS
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
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