The promyelocytic leukemia protein functions as a negative regulator of IFN-gamma signaling.

ABSTRACT: IFN-gamma is an immunomodulatory cytokine and uses the STAT-1alpha transcription factor to mediate gene expression. The promyelocytic leukemia (PML) protein regulates transcription as an activator or repressor, depending on the gene under investigation. Herein, we examined the influence of PML on IFN-gamma signaling, using PML wild-type (Pml(+/+)) and deficient (Pml(-/-)) mouse embryonic fibroblasts (MEF). Pml(-/-) MEF exhibit enhanced IFN-gamma-induced STAT-1alpha transcriptional activity compared with Pml(+/+) cells. Moreover, reconstitution of PML in Pml(-/-) MEF reduced STAT-1alpha transcriptional activity to levels comparable to Pml(+/+) MEF. Numerous endogenous IFN-gamma-regulated genes were up-regulated in Pml(-/-) MEF compared with Pml(+/+) MEF. IFN-gamma-mediated STAT-1alpha DNA-b

SUBMITTER: Choi YH 

PROVIDER: S-EPMC1693728 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature