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
Synonyms
IL-37(1-?) and IL-37 (?-) dissocates from IL-37(1-?):IL-37(?-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
11145836 IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp

Pan, G, Risser, P, Mao, W, Baldwin, DT, Zhong, AW, Filvaroff, E, Yansura, D, Lewis, L, Eigenbrot, C, Henzel, WJ, Vandlen, R

Cytokine 2001
18390730 The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines

Sharma, S, Kulk, N, Nold, MF, Gräf, R, Kim, SH, Reinhardt, D, Dinarello, CA, Bufler, P

J. Immunol. 2008
24481253 Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses

Bulau, AM, Nold, MF, Li, S, Nold-Petry, CA, Fink, M, Mansell, A, Schwerd, T, Hong, J, Rubartelli, A, Dinarello, CA, Bufler, P

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

Kumar, S, Hanning, CR, Brigham-Burke, MR, Rieman, DJ, Lehr, R, Khandekar, S, Kirkpatrick, RB, Scott, GF, Lee, JC, Lynch, FJ, Gao, W, Gambotto, A, Lotze, MT

Cytokine 2002
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