caspase-1; IL1 beta-converting enzyme [ICE] (CASP1, IL1BC, IL1BCE)
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Function
- thiol protease that cleaves inactive IL-1 beta between an Asp & Ala, releasing mature proinflammatory cytokine IL-1 beta
- may also be involved in processing of other cytokines including IL-6 & TNF-alpha
- substrate specificity for Asp-X
- role in for defense against pathogens
- cleaves sterol regulatory element binding proteins (SREBPs) & activates them.
- can promote apoptosis
- may be a component of the inflammasome
- interacts with INCA
- specifically inhibited by the cowpox virus Crma protein
- 2 subunits are derived from the precursor sequence by an autocatalytic mechanism
- strict requirement for an Asp residue at position P1 & has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|-
Structure
- heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kD (p20) & a 10 kD (p10) subunit.
- p20 subunit can also form a heterodimer with the epsilon isoform which then has an inhibitory effect
- belongs to the peptidase C14 family
- contains 1 CARD domain
Compartment
Alternative splicing
Expression
- synthesized principally in monocytes as an inactive proenzyme that autoprocesses to an active tetramer
- expressed in spleen & lung > liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney & testis
- no expression in the brain
Notes
- ICE is homologous to C. elegans ced-3 & represents a class of cysteine proteases important in apoptosis. Thymocytes from ICE -/- mice are sensitive to apoptosis induced by dexamethasone or ionizing radiation, but are resistant to apoptosis induced by Fas antibody[2]
- despite the defect in apoptosis, ICE -/- mice appear to develop normally
More general terms
More specific terms
Component of
References
- ↑ Wang L, Miura M, Bergeron L, Zhu H, Yuan J. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 1994 Sep 9;78(5):739-50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8087842
- ↑ 2.0 2.1 Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS, Flavell RA. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science. 1995 Mar 31;267(5206):2000-3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7535475
- ↑ Kumar S. ICE-like proteases in apoptosis. Trends Biochem Sci. 1995 May;20(5):198-202. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7610484
- ↑ Martin SJ, Green DR. Protease activation during apoptosis: death by a thousand cuts? Cell. 1995 Aug 11;82(3):349-52. Review. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7634323