Reactome | IL37(1-?) and IL37 (?-) dissocates from IL37(1-?):IL37(?-218):CASP1(120-197):CASP1(317-404)

IL37(1-?) and IL37 (?-) dissocates from IL37(1-?):IL37(?-218):CASP1(120-197):CASP1(317-404)

Stable Identifier

R-HSA-9012689

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

cytosol

Synonyms

IL-37(1-?) and IL-37 (?-) dissocates from IL-37(1-?):IL-37(?-218):CASP1(120-197):CASP1(317-404)

ReviewStatus

5/5

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IL37(1-?) and IL37 (?-) dissocates from IL37(1-?):IL37(?-218):CASP1(120-197):CASP1(317-404)

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Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tissues. Interleukin 37 (IL-37, IL-1 F7) is a member of the IL-1 family. There are five isoforms of IL-37 (a-e) of which transcript IL-37b is known to be functional (Sharma et al. 2008). This isoform is represented in UniProt as the canonical form of IL-37 and in Reactome as the full length, unprocessed form of IL-37. Like several other IL-1 family members, IL-37 is synthesized as a precursor that requires processing (primarily by caspase 1) to attain full receptor agonist or antagonist function. The putative caspase 1 cleavage site is at aspartic acid 20 (Kumar et al. 2002). However, other truncation sites in IL-37 have been suggested (Pan et al. 2001). Once processed, Caspase 1 dissociates from the protein. Caspase 1 may not be the only enzyme responsible for IL-37 processing (Sharma et al. 2008). These events ultimately lead to suppression of cytokine production in several types of immune cells resulting in reduced inflammation. This is a black box event because the cleavage sites and the enzymes responsible for the processing of IL-37 are uncertain.

Literature References

PubMed ID	Title	Journal	Year
18390730	The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines Dinarello, CA, Sharma, S, Bufler, P, Reinhardt, D, Kim, SH, Gräf, R, Nold, MF, Kulk, N	J. Immunol.	2008
11145836	IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp Filvaroff, E, Vandlen, R, Henzel, WJ, Pan, G, Risser, P, Yansura, D, Mao, W, Baldwin, DT, Lewis, L, Zhong, AW, Eigenbrot, C	Cytokine	2001
24481253	Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses Dinarello, CA, Bufler, P, Li, S, Rubartelli, A, Fink, M, Bulau, AM, Schwerd, T, Mansell, A, Nold, MF, Hong, J, Nold-Petry, CA	Proc. Natl. Acad. Sci. U.S.A.	2014
12096920	Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-gamma production Brigham-Burke, MR, Rieman, DJ, Kumar, S, Gambotto, A, Lotze, MT, Lehr, R, Kirkpatrick, RB, Lee, JC, Khandekar, S, Lynch, FJ, Hanning, CR, Scott, GF, Gao, W	Cytokine	2002