Reactome | IL37(?-218):p-S423,S425-SMAD3 translocates to the nucleus

IL37(?-218):p-S423,S425-SMAD3 translocates to the nucleus

Stable Identifier

R-HSA-9008928

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

Synonyms

IL-37(?-218):p-S423,S425-SMAD3 translocates to the nucleus

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IL37(?-218):p-S423,S425-SMAD3 translocates to the nucleus

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Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tissues. Interleukin 37 (IL 37), also known as IL 1F7, 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 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.

Literature References

PubMed ID	Title	Journal	Year
27060871	Suppression of innate inflammation and immunity by interleukin-37 Dinarello, CA, Nold-Petry, C, Nold, M, Fujita, M, Li, S, Kim, S, Bufler, P	Eur. J. Immunol.	2016
20935647	IL-37 is a fundamental inhibitor of innate immunity Nold, MF, Nold-Petry, CA, Zepp, JA, Palmer, BE, Bufler, P, Dinarello, CA	Nat. Immunol.	2010
15527767	Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity Grimsby, S, Jaensson, H, Dubrovska, A, Lomnytska, M, Hellman, U, Souchelnytskyi, S	FEBS Lett.	2004