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The roles of physiological and synthetic IAP antagonism on c-IAP1/2 degradation

 

The inhibitor of apoptosis proteins (IAP) play critical roles in variety cellular signaling pathways related to immune and inflammatory responses. Among the family members cellular inhibitor of apoptosis protein 1 and 2 (c-IAP1/2) are key regulators of NF-κB, which can induce degradation of c-IAP1/2 while activating. This non-canonical NF-κB pathway is activated by a limited subset of the tumor necrosis factor (TNF) receptor superfamily, including CD30, CD40 and TNFR2. Kocab et al. took a system approach to extensively compare the transcriptional programs triggered by CD30, which can degrade c-IAPs to SM-164, a synthetic IAP antagonist induces c-IAP degradation. The article was published in Oncogene.

 

Researchers used a technique called Bru-seq, which allows the specific analysis of newly transcribed RNA, for identification of gene expression profiles following each stimulus. Analysis of the profiles of CD30 activation and SM-164 treatment revealed differences between these two modes of IAP antagonism, indicating novel functions and consequences of c-IAP1/2 degradation, which was the downregulated expression of genes related to the ribosome and translation. The findings provide insight into the mechanism of SMs, as well as our understanding of their therapeutic potential. 

 

Reference:
Oncogene. 2015 Feb 9. doi: 10.1038/onc.2015.3.

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