期刊
CANCER CELL
卷 23, 期 4, 页码 435-449出版社
CELL PRESS
DOI: 10.1016/j.ccr.2013.02.017
关键词
-
资金
- National Institutes of Health, National Cancer Institute
- Center for Cancer Research
We performed a loss-of-function RNA interference screen to define therapeutic targets in multiple nnyeloma, 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 cFLIP(L) in nnyeloma, 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 myelorna 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.
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