Translational control of PML contributes to TNFα-induced apoptosis of MCF7 breast cancer cells and decreased angiogenesis in HUVECs.

ABSTRACT: The tumor suppressor protein promyelocytic leukemia (PML) is a key regulator of inflammatory responses and tumorigenesis and functions through the assembly of subnuclear structures known as PML nuclear bodies (NBs). The inflammation-related cytokine tumor necrosis factor-α (TNFα) is known to induce PML protein accumulation and PML NB formation that mediate TNFα-induced cell death in cancer cells and inhibition of migration and capillary tube formation in endothelial cells (ECs). In this study, we uncover a novel mechanism of PML gene regulation in which the p38 MAPK and its downstream kinase MAP kinase-activated protein kinase 1 (MNK1) mediate TNFα-induced PML protein accumulation and PML NB formation. The mechanism includes the presence of an internal ribosome entry site (IRES) found with

SUBMITTER: Hsu KS 

PROVIDER: S-EPMC5072441 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature