The cellular apoptosis susceptibility protein (CAS) promotes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis and cell proliferation Journal Article
| Authors: | Monian, P.; Jiang, X. |
| Article Title: | The cellular apoptosis susceptibility protein (CAS) promotes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis and cell proliferation |
| Abstract: | A signature event during the cell intrinsic apoptotic pathway is mitochondrial outer membrane permeabilization, leading to formation of the apoptosome, a caspase activation complex. The cellular apoptosis susceptibility protein (CAS) can facilitate apoptosome assembly by stimulating nucleotide exchange on Apaf-1 following binding of cytochrome c. We report here that CAS expression itself is up-regulated during tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, and knockdown of CAS renders cells resistant to TRAIL.We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation. We identified a novel signaling pathway whereby caspase-8 engages a feedforward cascade that leads to CAS up-regulation and amplifies the apoptotic signal. Furthermore, in silico analysis revealed that expression of CAS is up-regulated at both the mRNA and DNA levels in human breast tumors, consistent with its role in promoting cell proliferation. Overexpression of various oncogenes led to CAS upregulation in non-transformed cells. Intriguingly, oncogene-induced CAS up-regulation also resulted in greater susceptibility to TRAIL-induced cell death, consistent with its proapoptotic function. These findings suggest that CAS plays contrasting roles in proliferation and apoptosis and that overexpression of CAS in tumors could serve as a potential biomarker to guide therapeutic choices. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. |
| Keywords: | cell proliferation; proteins; cytology; cell death; tumors; nucleic acids; ligands; macrophages; glycoproteins; signaling pathways; cells; nucleotide exchange; oncogenic viruses; proteasomal degradation; post-transcriptional; pro-apoptotic function; proliferation and apoptosis; susceptibility proteins; tumor necrosis factor-related apoptosis-inducing ligands |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 291 |
| Issue: | 5 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2016-01-29 |
| Start Page: | 2379 |
| End Page: | 2388 |
| Language: | English |
| DOI: | 10.1074/jbc.M115.685008 |
| PROVIDER: | scopus |
| PMCID: | PMC4732220 |
| PUBMED: | 26668314 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 March 2016 -- Source: Scopus |
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