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Control of Autophagic Cell Death by Caspase-10 in Multiple Myeloma.
- Source :
-
Cancer Cell . Apr2013, Vol. 23 Issue 4, p435-449. 15p. - Publication Year :
- 2013
-
Abstract
- Summary: We performed a loss-of-function RNA interference screen to define therapeutic targets in multiple myeloma, a genetically diverse plasma cell malignancy. Unexpectedly, we discovered that all myeloma lines require caspase-10 for survival irrespective of their genetic abnormalities. The transcription factor IRF4 induces both caspase-10 and its associated protein cFLIPL in myeloma, generating a protease that does not induce apoptosis but rather blocks an autophagy-dependent cell death pathway. Caspase-10 inhibits autophagy by cleaving the BCL2-interacting protein BCLAF1, itself a strong inducer of autophagy that acts by displacing beclin-1 from BCL2. While myeloma cells require a basal level of autophagy for survival, caspase-10 tempers this response to avoid cell death. Drugs that disrupt this vital balance may have therapeutic potential in myeloma. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 23
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 89070449
- Full Text :
- https://doi.org/10.1016/j.ccr.2013.02.017