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PMID:22274400

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Citation

Feoktistova, M, Geserick, P, Panayotova-Dimitrova, D and Leverkus, M (2012) Pick your poison: the Ripoptosome, a cell death platform regulating apoptosis and necroptosis. Cell Cycle 11:460-7

Abstract

At an unbelievable pace, recent evidence has emerged that demonstrates the importance of a programmed form of necrosis (necroptosis) in physiology, pathophysiology and embryonic development. It is clear that the understanding of the intracellular control of necroptosis as compared to caspase-dependent apoptosis is of paramount importance. Tumorigenesis, immune surveillance of cancer and pathogen-induced disease, to name only a few, appear to be affected by the mode of cell death in vivo. Here, we discuss the Ripoptosome, a newly defined 2 MDa intracellular signalling complex that can be formed upon genotoxic stress or loss of inhibitor-of apoptosis proteins (IAPs). The Ripoptosome is a signaling platform that can switch modes between apoptotic and necroptotic cell death. In this report, we extend our recent studies and further the notion that the stoichiometric balance between RIP1 and cIAPs is critical for Ripoptosome formation. Furthermore, we demonstrate the critical relevance of the balance of expression levels of short (cFLIPS) or viral (vFLIP) forms of FLIP and RIP3 kinase for the spontaneous execution of necroptosis whenever cIAPs are absent in the cells. Our study thus supports and extends the intriguing role of the Ripoptosome for the regulation of apoptosis and necroptosis.

Links

PubMed Online version:10.4161/cc.11.3.19060

Keywords

Apoptosis/physiology; CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism; Caspase 8/metabolism; Cell Line, Tumor; Fas Ligand Protein/metabolism; Humans; Inhibitor of Apoptosis Proteins/antagonists & inhibitors; Inhibitor of Apoptosis Proteins/metabolism; Necrosis/metabolism; Necrosis/pathology; Nuclear Pore Complex Proteins/genetics; Nuclear Pore Complex Proteins/metabolism; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Receptor-Interacting Protein Serine-Threonine Kinases/genetics; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism; Signal Transduction; Toll-Like Receptor 3/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FADD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14790

F

Seeded From UniProt

complete

HUMAN:RIPK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14790

F

Seeded From UniProt

complete

HUMAN:RIPK1

involved_in

GO:2001238: positive regulation of extrinsic apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_participant:(UniProtKB:Q14790)
  • has_participant:(UniProtKB:Q13158)
  • has_participant:(UniProtKB:Q13490)

Seeded From UniProt

complete

HUMAN:RIPK1

involved_in

GO:0060545: positive regulation of necroptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_participant:(UniProtKB:Q14790)
  • has_participant:(UniProtKB:Q13158)
  • has_participant:(UniProtKB:Q13490)

Seeded From UniProt

complete

HUMAN:CASP8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13158

F

Seeded From UniProt

complete

HUMAN:CASP8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13546

F

Seeded From UniProt

complete

MCV1:CFLA

involved_in

GO:0060545: positive regulation of necroptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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