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Translational control of PML contributes to TNFα-induced apoptosis of MCF7 breast cancer cells and decreased angiogenesis in HUVECs
- Source :
- Cell Death and Differentiation
- Publication Year :
- 2014
-
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 within the well-conserved 100 nucleotides upstream of the PML initiation codon. The activity of the PML IRES is induced by TNFα in a manner that involves MNK1 activation. It is proposed that the p38-MNK1-PML network regulates TNFα-induced apoptosis in breast cancer cells and TNFα-mediated inhibition of migration and capillary tube formation in ECs.
- Subjects :
- 0301 basic medicine
Angiogenesis
viruses
Neovascularization, Physiologic
Apoptosis
Breast Neoplasms
HL-60 Cells
Internal Ribosome Entry Sites
Promyelocytic Leukemia Protein
Protein Serine-Threonine Kinases
medicine.disease_cause
p38 Mitogen-Activated Protein Kinases
03 medical and health sciences
Promyelocytic leukemia protein
Matrix Metalloproteinase 10
Cell Movement
medicine
Human Umbilical Vein Endothelial Cells
Humans
Nuclear protein
Protein kinase A
Molecular Biology
Chemokine CCL2
Cell Proliferation
Original Paper
biology
Tumor Necrosis Factor-alpha
Tumor Suppressor Proteins
Intracellular Signaling Peptides and Proteins
virus diseases
Nuclear Proteins
Cell Biology
Virology
3. Good health
Cell biology
Gene Expression Regulation, Neoplastic
Internal ribosome entry site
030104 developmental biology
Protein Biosynthesis
Cancer cell
biology.protein
MCF-7 Cells
Tumor necrosis factor alpha
Carcinogenesis
5' Untranslated Regions
Transcription Factors
Subjects
Details
- ISSN :
- 14765403
- Volume :
- 23
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell death and differentiation
- Accession number :
- edsair.doi.dedup.....618dac13daca8c80613c47ef5dacf7a0