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Oncogene
Article
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Oncogene
Article . 1998 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
Oncogene
Article . 1999
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The inhibitors of apoptosis (IAPs) and their emerging role in cancer

Authors: E C, LaCasse; S, Baird; R G, Korneluk; A E, MacKenzie;

The inhibitors of apoptosis (IAPs) and their emerging role in cancer

Abstract

The inhibitor of apoptosis protein family has been characterized over the past 5 years, initially in baculovirus and more recently in metazoans. The IAPs are a widely expressed gene family of apoptotic inhibitors from both phylogenic and physiologic points of view. The diversity of triggers against which the IAPs suppress apoptosis is greater than that observed for any other family of apoptotic inhibitors including the bcl-2 family. The central mechanisms of IAP apoptotic suppression appear to be through direct caspase and pro-caspase inhibition (primarily caspase 3 and 7) and modulation of and by the transcription factor NF-kappaB. Although evidence for a direct oncogenic role for the IAPs has yet to be delineated, a number of lines of evidence point towards this class of protein playing a role in oncogenesis. The strongest evidence for IAP involvement in cancer is seen in the IAP called survivin. Although not observed in adult differentiated tissue, survivin is present in most transformed cell lines and cancers tested to date. Survivin has been shown to inhibit caspase directly and apoptosis in general, moreover survivin protein levels correlate inversely with 5 year survival rates in colorectal cancer. Recent data has also implicated survivin in cell cycle control. The second line of evidence for IAP involvement in cancer comes from their emerging role as mediators and regulators of the anti-apoptotic activity of v-Rel and NF-kappaB transcription factor families. The IAPs have been shown to be induced by NF-kappaB or v-Rel in multiple cell lines and conversely, HIAP1 and HIAP2 have been shown to activate NF-kappaB possibly forming a positive feed-back loop. Overall a picture consistent with an IAP role in tumour progression rather than tumour initiation is emerging making the IAPs an attractive therapeutic target.

Keywords

Oncogene Proteins v-rel, Sequence Homology, Amino Acid, Survivin, Molecular Sequence Data, Retroviridae Proteins, Oncogenic, NF-kappa B, Proteins, Apoptosis, Protein-Tyrosine Kinases, Inhibitor of Apoptosis Proteins, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Caspases, Neoplasms, Protein Biosynthesis, Animals, Humans, Amino Acid Sequence, Microtubule-Associated Proteins, Transcription Factors

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    962
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    influence
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Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
962
Top 1%
Top 0.1%
Top 0.1%
bronze