XIAP as a regulator of inflammatory cell death: the TNF and RIP3 angle
Monica Yabal1, Philipp J Jost1
1III. Medizinische Klink; Klinikum rechts der Isar; Technische Universität München ; Germany.
Molecular & Cellular Oncology
|June 17, 2016
Abstract:
There is currently immense interest in understanding the biological consequences of aberrant necroptosis. The recently uncovered role for X-linked inhibitor of apoptosis protein (XIAP) in blocking tumor necrosis factor-dependent necroptosis explains, at least in part, the systemic hyperinflammatory syndrome XLP-2. However, it also points to rather unexpected differences between XIAP and the related proteins baculoviral IAP repeat containing 2 and 3 (cIAP1/2).
Insights
Aberrant necroptosis has significant biological consequences. X-linked inhibitor of apoptosis protein (XIAP) blocks tumor necrosis factor-dependent necroptosis, explaining XLP-2, but reveals differences from cellular IAP proteins.
Area of Science:
- Molecular Biology
- Immunology
- Cell Death Research
Background:
- Necroptosis, a regulated form of necrosis, is implicated in various diseases.
- The X-linked inhibitor of apoptosis protein (XIAP) is a key regulator in cellular processes.
- Systemic autoinflammatory diseases, such as XLP-2, involve dysregulated immune responses.
Purpose of the Study:
- To elucidate the biological consequences of aberrant necroptosis.
- To investigate the role of X-linked inhibitor of apoptosis protein (XIAP) in necroptosis.
- To understand the molecular basis of XLP-2 by examining XIAP's function.
Main Methods:
- Analysis of tumor necrosis factor (TNF)-dependent signaling pathways.
- Biochemical assays to study protein interactions and functions.
- Comparison of XIAP with related baculoviral IAP repeat containing proteins (cIAP1/2).
Main Results:
- XIAP was found to block tumor necrosis factor-dependent necroptosis.
- This inhibitory role of XIAP contributes to the pathogenesis of XLP-2.
- Unexpected functional distinctions were identified between XIAP and cIAP1/2.
Conclusions:
- XIAP plays a critical role in preventing excessive necroptosis and associated inflammation.
- Understanding XIAP's function provides insights into XLP-2 and related hyperinflammatory syndromes.
- The differences between XIAP and cIAP1/2 highlight the specificity of IAP proteins in regulating cell death.
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