Regulation of NF-?B by PML and PML-RAR?.

ABSTRACT: Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNF?-induced transcriptional responses by promoting NF-?B activity. TNF?-treated PML-/- cells show normal I?B? degradation and NF-?B nuclear translocation but significantly reduced NF-?B DNA binding and phosphorylation of NF-?B p65. We also demonstrate that the PML retinoic acid receptor-? (PML-RAR?) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNF? induced gene expression and phosphorylation of NF-?B. This study establishes PML as an important regulator of NF-?B and demonstrates that PML-RAR? dysregulates NF-?B.

SUBMITTER: Ahmed A 

PROVIDER: S-EPMC5357907 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature