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Overview
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Background
SIMPL, also known as IRAK1BP1 (interleukin-1 receptor-associated kinase 1-binding protein 1), is a 260 amino acid protein belonging to the IRAK1BP1 family. In addition to containing an intrinsically disordered region which associates with HSPA1 and HSPA8, SIMPL also interacts directly with IRAK1 and promotes RELA transcriptional activity. SIMPL is a major component of the IRAK1-dependent TNFRSF1A signaling pathway in which TNF-alpha induces NF-kappa-B gene transcription, leading to an inhibition of proinflammatory cytokines. Inactivation of SIMPL inhibits tumor necrosis factor receptor type I-induced NF-kappaB activity. Localizing to the nucleus and cytoplasm, SIMPL requires the phosphorylation of Ser-56 and/or Ser-62 to be fully active.
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