Recent advances in understanding inhibitor of apoptosis proteins

Najoua Lalaoui; David Lawrence Vaux

doi:10.12688/f1000research.16439.1

Recent advances in understanding inhibitor of apoptosis proteins

F1000Res. 2018 Dec 3:7:F1000 Faculty Rev-1889. doi: 10.12688/f1000research.16439.1. eCollection 2018.

Authors

Najoua Lalaoui^{1

2}, David Lawrence Vaux^{1

2}

Affiliations

¹ Cell Signalling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3052, Australia.
² Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, 3050, Australia.

Abstract

The inhibitor of apoptosis proteins (IAPs) are a family of proteins that were chiefly known for their ability to inhibit apoptosis by blocking caspase activation or activity. Recent research has shown that cellular IAP1 (cIAP1), cIAP2, and X-linked IAP (XIAP) also regulate signaling by receptors of the innate immune system by ubiquitylating their substrates. These IAPs thereby act at the intersection of pathways leading to cell death and inflammation. Mutation of IAP genes can impair tissue homeostasis and is linked to several human diseases. Small-molecule IAP antagonists have been developed to treat certain malignant, infectious, and inflammatory diseases. Here, we will discuss recent advances in our understanding of the functions of cIAP1, cIAP2, and XIAP; the consequences of their mutation or dysregulation; and the therapeutic potential of IAP antagonist drugs.

Keywords: IAP; cell death; inflammation; innate receptors signalling; smac-mimetic.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cell Death
Humans
Immunity, Innate
Inflammation
Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
Inhibitor of Apoptosis Proteins / genetics
Inhibitor of Apoptosis Proteins / physiology*
Mutation

Substances

Inhibitor of Apoptosis Proteins

Grants and funding

This work was supported by project grant #1145588 from the Cancer Australia and Cure Cancer Australia Foundation (to NL), Victorian Cancer Agency Mid-career Fellowship #17030 (to NL), Australian National Health and Medical Research Council (NHMRC) Program Grant #1113133 (to DLV), NHMRC Fellowship #1020136 (to DLV), and Leukemia and Lymphoma Society SCOR grant #7001-13 (to DLV). This work was made possible by operational infrastructure grants through the Australian government’s Independent Research Institute Infrastructure Support Scheme and the Victorian state government’s Operational Infrastructure Support.