IAPs, their Antagonists and their Role in Neurological Disease and Cancer

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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IAPs, their Antagonists and their Role in Neurological Disease and Cancer



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 4(4): 393-406.

Author(s): Robert E. Gerl and Anne M Verhagen.

Affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville Victoria 3050, Australia.

Abstract

Apoptosis is a noninflammatory process used by multicellular organisms to eliminate unwanted cells. It is implemented by a family of cysteine proteases called caspases through their cleavage of cellular proteins. The upstream events leading to caspase activation are controlled at multiple levels by an extensive array of proteins, including death receptors, adapters, transcription factors and Bcl-2 family members, while acting downstream to curb caspase activity are the inhibitor of apoptosis proteins (IAPs). Since their initial discovery much has been learned about how IAPs regulate cell death and are themselves regulated. Structural studies have given us insight into how IAPs interact with and neutralise caspase activity, proteomic approaches have uncovered IAP interacting molecules, such as DIABLO/SMAC, that can antagonise IAP function, and additional modes of IAP regulation at the transcriptional and post translational level have been identified. Their potential involvement in conferring cancer cell resistance to apoptotic stimuli, e.g. chemotherapeutic drugs, has presented them as plausible targets for cancer therapy. Conversely, they may be beneficial in protecting neuronal cells from inappropriate apoptosis observed in many different neurological diseases. What follows is a discussion of the various mammalian IAPs and other BIR domain containing proteins (BIRPs), focussing on their structure, function and regulation by antagonists as well as their possible involvement in disease processes.

Keywords:

apoptosis, diablo/Smac, nk cells, baculovirus Iap repeat (bir), hippocampal neurons, caspase.



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Article Details

Volume: 4
Issue Number: 4
First Page: 393
Last Page: 406
Page Count: 14
DOI: 10.2174/1568014054546272
Price: $58
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