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

被引：28
作者：
Hsu, K-S [1 ]
Guan, B-J [2 ]
Cheng, X. [1 ]
Guan, D. [1 ]
Lam, M. [3 ]
Hatzoglou, M. [2 ]
Kao, H-Y [1 ,4 ,5 ]
机构：
[1] Case Western Reserve Univ, Dept Biochem, 10900 Euclid Ave, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA
[3] Univ Hosp Case Med Ctr, Dept Dermatol, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Ctr Comprehens Canc, 10900 Euclid Ave, Cleveland, OH 44106 USA
[5] Univ Hosp Cleveland, 10900 Euclid Ave, Cleveland, OH 44106 USA
来源：
CELL DEATH AND DIFFERENTIATION | 2016年 / 23卷 / 03期
关键词：
TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ACTIVATED PROTEIN-KINASES; RIBOSOME ENTRY SITES; INITIATION-FACTOR; 4E; NUCLEAR-BODY; ENDOPLASMIC-RETICULUM; PREMATURE SENESCENCE; SUPPRESSOR PML; PHOSPHORYLATION;
D O I：
10.1038/cdd.2015.114
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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-alpha (TNF alpha) is known to induce PML protein accumulation and PML NB formation that mediate TNF alpha-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 TNF alpha-induced PML protein accumulation and PML NB formation. The mechanism includes the presence of an internal ribosome entry site (IRES) found within the well-conserved 100 nucleotides upstream of the PML initiation codon. The activity of the PML IRES is induced by TNF alpha in a manner that involves MNK1 activation. It is proposed that the p38-MNK1-PML network regulates TNF alpha-induced apoptosis in breast cancer cells and TNF alpha-mediated inhibition of migration and capillary tube formation in ECs.
引用
收藏
页码：469 / 483
页数：15
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