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Inhibitor of apoptosis proteins as intracellular signaling intermediates
Andrew J Kocab1,2, Colin S Duckett2,3
1Graduate Program in Immunology, The University of Michigan, Ann Arbor, MI, USA.
Abstract:
Inhibitor of apoptosis (IAP) proteins have often been considered inhibitors of cell death due to early reports that described their ability to directly bind and inhibit caspases, the primary factors that implement apoptosis. However, a greater understanding is evolving regarding the vital roles played by IAPs as transduction intermediates in a diverse set of signaling cascades associated with functions ranging from the innate immune response to cell migration to cell-cycle regulation. In this review, we discuss the functions of IAPs in signaling, focusing primarily on the cellular IAP (c-IAP) proteins. The c-IAPs are important components in tumor necrosis factor receptor superfamily signaling cascades, which include activation of the NF-κB transcription factor family. As these receptors modulate cell proliferation and cell death, the involvement of the c-IAPs in these pathways provides an additional means of controlling cellular fate beyond simply inhibiting caspase activity. Additionally, IAP-binding proteins, such as Smac and caspases, which have been described as having cell death-independent roles, may affect c-IAP activity in intracellular signaling. Collectively, the multi-faceted functions and complex regulation of the c-IAPs illustrate their importance as intracellular signaling intermediates.
Insights
Inhibitors of apoptosis (IAPs) are more than cell death inhibitors; they are key signaling intermediates in immune response and cell cycle regulation. Cellular IAPs (c-IAPs) critically regulate cell fate via NF-κB pathways.
Area of Science:
- Cell Biology
- Molecular Signaling
- Immunology
Background:
- Inhibitors of apoptosis (IAPs) were initially recognized for their direct inhibition of caspases, crucial executioners of apoptosis.
- Emerging evidence highlights IAPs' broader roles as signaling intermediates in diverse cellular processes.
Purpose of the Study:
- To review the multifaceted functions of IAPs, with a focus on cellular IAPs (c-IAPs) in intracellular signaling.
- To explore the involvement of c-IAPs in tumor necrosis factor receptor superfamily signaling and NF-κB activation.
Main Methods:
- Literature review focusing on IAP protein functions in cellular signaling pathways.
- Analysis of the role of c-IAPs in TNF receptor superfamily signaling cascades.
Main Results:
- IAPs act as vital transduction intermediates in signaling cascades, influencing innate immunity, cell migration, and cell-cycle regulation.
- c-IAPs are integral to tumor necrosis factor receptor superfamily signaling, including NF-κB pathway activation.
- IAP-binding proteins like Smac and caspases exhibit cell death-independent roles impacting c-IAP activity.
Conclusions:
- The functions of c-IAPs extend beyond caspase inhibition, offering additional control over cellular fate.
- IAPs are complex regulators of intracellular signaling, crucial for diverse cellular functions and fate determination.
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