Apoptosis of lymphoma cells is abolished due to blockade of cytochrome <Emphasis Type="Italic">c</Emphasis> release despite Nur77 mitochondrial targeting |
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Authors: | Andrzej Rapak Izabela Stasik Ewa Ziolo Leon Strzadala |
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Institution: | (1) Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wroclaw, Poland |
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Abstract: | Nur77 is reported to undergo translocation to mitochondria in response to apoptotic signaling in a variety of cancer cell
lines. It was shown that on the mitochondrial membrane, Nur77 interacts with Bcl-2, leading to the conversion of this protein
from a protector to a killer with subsequent release of cytochrome c to the cytosol. Here it is shown that in thymic lymphoma cells resistant to calcium-mediated apoptosis, cytochrome c release is abolished despite of Nur77 mitochondrial targeting. However, cytochrome c release and apoptosis can be restored by treatment with FK506. Hence, the molecular target regulation of the sensitivity
of lymphoma cells to calcium signaling is associated with cytochrome c release and is FK506 sensitive. These results provide new insight into the role of FK506-sensitive factors as a critical
link between calcium signaling and resistance of lymphoma cells to death. |
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Keywords: | Apoptosis Lymphoma Nur77 FK506 Mitochondria Cytochrome c |
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