Apoptosis of lymphoma cells is abolished due to blockade of cytochrome c release despite Nur77 mitochondrial targeting.
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.
Rapak
Andrzej
A
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114, Wroclaw, Poland.
Stasik
Izabela
I
Ziolo
Ewa
E
Strzadala
Leon
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016559:Tacrolimus / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D045304:Cytochromes c; D016559:Tacrolimus