v-Rel prevents apoptosis in transformed lymphoid cells and blocks TNFalpha-induced cell death.
The v-Rel oncoprotein belongs to the Rel/NF-kappaB family of transcription factors. It transforms chicken lymphoid cells in vitro and induces fatal lymphomas in vivo. In this study, we used a tetracycline-regulated system to characterize the role of v-Rel in cell transformation. We show that the continued expression of v-Rel is necessary to maintain the viability of transformed lymphoid cells and enables primary spleen cells to escape apoptosis in vitro culture. In agreement with a possible role for v-Rel in the inhibition of programmed cell death, its inducible expression in HeLa cells prevented TNFalpha-induced apoptosis. While the repression of v-Rel was accompanied by the rapid degradation of IkappaBalpha, changes in the steady-state levels of the apoptosis inhibitors Bcl-2 and Bcl-X(L) were only observed following the onset of cell death in transformed lymphoid cells. This suggests that the anti-apoptotic activity of v-Rel may affect other apoptosis inhibitors or other factors in the death pathway. Together, these findings demonstrate that v-Rel blocks apoptosis and suggest that this activity may be an important component of its transforming function.
Zong
W X
WX
Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5638, USA.
Farrell
M
M
Bash
J
J
Gélinas
C
C
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002645:Chickens; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic / Q000494:pharmacology / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D013752:Tetracycline