Human Interaction Network Ontology

Last uploaded: June 27, 2014
Preferred Name

Interleukin-1 processing
Synonyms
Definitions

Authored: Ray, KP, 2010-05-17 The IL-1 family of cytokines that interact with the Type 1 IL-1R include IL-1 Alpha (IL1A), IL-1 Beta (IL1B) and the IL-1 receptor antagonist protein (IL1RAP). IL1RAP is synthesized with a signal peptide and secreted as a mature protein via the classical secretory pathway. IL1A and IL1B are synthesised as cytoplasmic precursors (pro-IL1A and pro-IL1B) in activated cells. They have no signal sequence, precluding secretion via the classical ER-Golgi route (Rubartelli et al. 1990). Processing of pro-IL1B to the active form requires caspase-1 (Thornberry et al. 1992), which is itself activated by a molecular scaffold termed the inflammasome (Martinon et al. 2002). Processing and release of IL1B are thought to be closely linked, because mature IL1B is only seen inside inflammatory cells just prior to release (Brough et al. 2003). It has been reported that in monocytes a fraction of cellular IL1B is released by the regulated secretion of late endosomes and early lysosomes, and that this may represent a cellular compartment where caspase-1 processing of pro-IL1B takes place (Andrei et al. 1999). Shedding of microvesicles from the plasma membrane has also been proposed as a mechanism of secretion (MacKenzie et al. 2001). These proposals superceded previous models in which non-specific release due to cell lysis and passage through a plasma membrane pore were considered. However, there is evidence in the literature that supports all of these mechanisms and there is still controversy over how IL1B exits from cells (Brough & Rothwell 2007). A calpain-like potease has been reported to be important for the processing of pro-IL1A, but much less is known about how IL1A is released from cells and what specific roles it plays in biology. Edited: Jupe, S, 2010-08-06 Reviewed: Pinteaux, E, 2010-09-06

ID

http://purl.obolibrary.org/obo/HINO_0022223

comment

Authored: Ray, KP, 2010-05-17

The IL-1 family of cytokines that interact with the Type 1 IL-1R include IL-1 Alpha (IL1A), IL-1 Beta (IL1B) and the IL-1 receptor antagonist protein (IL1RAP). IL1RAP is synthesized with a signal peptide and secreted as a mature protein via the classical secretory pathway. IL1A and IL1B are synthesised as cytoplasmic precursors (pro-IL1A and pro-IL1B) in activated cells. They have no signal sequence, precluding secretion via the classical ER-Golgi route (Rubartelli et al. 1990). Processing of pro-IL1B to the active form requires caspase-1 (Thornberry et al. 1992), which is itself activated by a molecular scaffold termed the inflammasome (Martinon et al. 2002). Processing and release of IL1B are thought to be closely linked, because mature IL1B is only seen inside inflammatory cells just prior to release (Brough et al. 2003). It has been reported that in monocytes a fraction of cellular IL1B is released by the regulated secretion of late endosomes and early lysosomes, and that this may represent a cellular compartment where caspase-1 processing of pro-IL1B takes place (Andrei et al. 1999). Shedding of microvesicles from the plasma membrane has also been proposed as a mechanism of secretion (MacKenzie et al. 2001). These proposals superceded previous models in which non-specific release due to cell lysis and passage through a plasma membrane pore were considered. However, there is evidence in the literature that supports all of these mechanisms and there is still controversy over how IL1B exits from cells (Brough & Rothwell 2007). A calpain-like potease has been reported to be important for the processing of pro-IL1A, but much less is known about how IL1A is released from cells and what specific roles it plays in biology.

Edited: Jupe, S, 2010-08-06

Reviewed: Pinteaux, E, 2010-09-06

definition source

Pubmed15530394

Pubmed12626557

Reactome, http://www.reactome.org

Pubmed17284521

Pubmed10233156

Pubmed1574116

Pubmed2328723

Pubmed11728343

label

Interleukin-1 processing

located_in

http://purl.obolibrary.org/obo/NCBITaxon_9606

prefixIRI

HINO:0022223

prefLabel

Interleukin-1 processing

seeAlso

ReactomeREACT_23950

Reactome Database ID Release 43448706

subClassOf

http://purl.obolibrary.org/obo/INO_0000021

has_part

http://purl.obolibrary.org/obo/HINO_0007232

http://purl.obolibrary.org/obo/HINO_0007230

http://purl.obolibrary.org/obo/HINO_0007226

http://purl.obolibrary.org/obo/HINO_0007225

http://purl.obolibrary.org/obo/HINO_0007228

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