Interleukin-37 signaling

Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tis-sues. 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 IL37 are uncertain. Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tis-sues. Interleukin 37 (IL 37), also known IL 1F7, is a the IL 1 family. There are five isoforms IL 37 (a e) of transcript IL IL 1 family IL 37b decapentaplegic homolog SMAD4 and this complex modulates the transcription of several genes downstream. Processed IL 37b can bind with phosphorylated SMAD3 in the cytosol of A549 cells M 2010, Grimsby This complex may then translocate from the cytosol to the nucleus and may affect the function of SMAD3. 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 SMAD3 assisted IL-37 translocation to the nucleus is not fully understood.


Interleukin-37 signaling ↗ Stable identifier: R-HSA-9008059
Compartments: cytosol, plasma membrane, extracellular region Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tissues. Interleukin 37 (IL37), also known as IL 1F7, is a member of the IL 1 family . Isoform b of IL37 (referred just as IL37) is synthesized as a precursor that requires processing (primarily by caspase 1) to attain full receptor agonist or antagonist function (Kumar et al. 2002). Both full length and processed IL37 can bind to the IL 18 binding protein (IL 18BP) and the Interleukin 18 receptor 1 (IL 18R1) (Shi et al. 2003). Upon binding to the IL18R1, IL37 recruits Single Ig IL 1 related receptor (SIGIRR) (Nold- . The IL37:IL18R1 complex can activate phosphorylation of Signal transducer and activator of transcription 3 (STAT3), Tyrosine protein kinase Mer and Phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase and dual specificity protein phosphatase PTEN and can also inhibit Nuclear factor NF kappa B p105 subunit (NFKB) . Processed IL37 can be secreted from the cytosol to the extracellular space or translocated into the nucleus (Bulau et al. 2014). Full length IL37 can also be secreted from the cytosol to the extracellular space (Bulau et al. 2014). Processed IL37 can bind with Mothers against decapentaplegic homolog 3 (SMAD3) in the cytosol and then translocate to the nucleus, where it facilitates transcription of Tyrosine protein phosphatase non receptors (PTPNs) (Nold et al. 2010, Luo et al. 2017. These events ultimately lead to suppression of cytokine production in several types of immune cells resulting in reduced inflammation. Dinarello, CA., Italiani, P., Pfaller, T., Pixner, C., Nold, MF., Lucchesi, D. et al. (2011) of which transcript IL-37b is known to be functional ). 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.

Literature references
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 processing of IL-37 begins by the binding of Caspase to the protein. This is a black box event because the precise Caspase binding site in IL-37 is unclear.
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). Caspase 1 may not be the only enzyme responsible for IL-37 processing ). This is a black box event because the cleavage sites and the enzymes responsible for the processing of IL-37 are uncertain. of which transcript IL-37b is known to be functional ). 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 of IL 37 (a e) of which transcript IL 37b is known to be functional (Sharma S et al., 2008). Like several other IL 1 family members, IL 37b is synthesized as precursors that require processing (primarily by caspase 1) to attain full receptor agonist or antagonist function (Kumar S et al., 2002). Mothers against decapentaplegic homolog 3 (SMAD3) binds SMAD4 and this complex modulates the transcription of several genes downstream. Processed IL 37b can bind with phosphorylated SMAD3 in the cytosol of A549 cells (Nold M F et al., 2010, Grimsby S et al., 2004. This complex may then translocate from the cytosol to the nucleus (Nold M F et al., 2010, Dinarello et al. 2016) and may affect the function of SMAD3. 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 SMAD3 assisted IL-37 translocation to the nucleus is not fully understood. of which transcript IL-37b is known to be functional ). 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.  of which transcript IL-37b is known to be functional ). 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