<unk> carries out independent attacks on many distinct cell organelles, including mitochondria, proteasomes, and histones, and interferes with cell processes such as macroautophagy. It has been shown that<unk> binds to the cell surface and rapidly invades cells, with tumor cells taking up far more protein than healthy, differentiated cells. The mechanism of its entry is poorly understood, but recent studies indicate that the oleic acid in the<unk> complex interacts with phosphatidylserine and o-glycosylated mucin on the plasma membrane, both of which are expressed in greater amounts on the plasma membrane of tumor cells, possibly providing for<unk> s specificity. One of the most prominent targets of<unk> once inside the cell is the mitochondrion. Electron microscopy has revealed physical damage to the mitochondrial membranes and assays have found cytochrome c release and activation of the caspase cascade, the most notable ones being caspases 2, 3, and 9. Cell death is not prevented by caspase inhibitors, or by BCL-2 or p53 mutagenesis, indicating that the traditional apoptotic caspase cascade is not the ultimate cause of cell death. Another target of<unk> is the proteasome. 26S proteasomes are activated in response to large quantities of unfolded<unk> protein in the cytoplasm, but degradation of<unk> by the proteasome is unusually slow. Furthermore, in vitro studies have shown that<unk> is capable of binding the catalytic 20S subunit of the proteasome and disabling its enzymatic activity, an effect that has never before been demonstrated for any protein. However, proteasome inhibition alone does not seem to be responsible for<unk> induced cell death, as proteasome inhibitors have been shown to reduce the cytotoxicity of<unk> <unk> also targets the nucleus, where it interacts with histones to interfere with transcriptional processes. Studies have shown that<unk> is mostly localized to the nucleus within one hour of invading a tumor cell.<unk> has been shown to bind with high affinity to individual histone proteins, to be specific H2a, H2b, H3, and H4, as well as entire nucleosomal units. This interaction irreversibly blocks transcription and leads to activation of p53. This process has been demonstrated to be similar to histone hyperacetylation and it was found that histone de-acetylase inhibitors potentiated the effects of<unk> <unk> cells showed the physiological characteristics of macroautophagy, a process in which cellular components are sequestered in double membrane-bound vesicles that fuse with lysosomes for degradation. Cells also showed decreased levels of mTOR, a known inhibitor of macroautophagy.<unk> cells and cells under conditions of amino acid starvation (a known initiator of macroautophagy) showed similar expression patterns of autophagocytotic proteins and responded equally well to addition of macroautophagy inhibitors.
HAMLET 
ZF2001
DEBRA
ABL 
ICE 
BRA
ESKAPE
CoWIN