Interferon (IFN) regulatory factor-1 (IRF-1) deregulation in ras-transformed mouse fibroblasts (RS485) was studied. Treatment with the proteasome inhibitor MG132 did not alter the constitutive IRF-1 protein levels in RS485 but significantly increased them in nontransformed NIH 3T3 cells at 4 h after serum stimulation of synchronized cultures. Because IRF-1 protein levels in NIH 3T3 are minimal at 4 h after serum starvation, the cyclic expression of IRF-1 in NIH 3T3 appears to be partially due to proteasome activity; however, proteasome activity in RS485 did not appear to be defective. In NIH 3T3 and RS485 cells treated with cycloheximide, there were similar rapid drops in IRF-1 protein levels, and the addition of MG132 along with cycloheximide prevented protein loss in both cell lines. Northern blot analyses of synchronized cultures showed that the IRF-1 message closely mirrored the protein expression pattern in both NIH 3T3 and RS485 cells. In synchronized cells treated with the transcription inhibitor actinomycin D, IRF-1 mRNA half-life was only marginally longer in ras-transformed fibroblasts than in the nontransformed cells, and this difference would contribute minimally to protein overexpression. These findings indicate that IRF-1 deregulation in RS485 cells occurs primarily at the transcriptional level. © Mary Ann Liebert, Inc.
CITATION STYLE
Attard, F. A., Contente, S., Yeh, T. J. A., Buchhagen, D. L., & Friedman, R. M. (2005). Mechanisms of deregulation of IFN regulatory factor-1 in ras-transformed fibroblasts. Journal of Interferon and Cytokine Research, 25(7), 418–423. https://doi.org/10.1089/jir.2005.25.418
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