Sep 5, 2017

Atf3 deficiency promotes genome instability and spontaneous tumorigenesis in mice

Oncogene
Z WangC Yan

Abstract

Mice lacking genes involving in the DNA-damage response (DDR) are often tumor prone owing to genome instability caused by oncogenic challenges. Previous studies demonstrate that activating transcription factor 3 (ATF3), a common stress sensor, can activate the tumor suppressor p53 and regulate expression of p53 target genes upon DNA damage. However, whether ATF3 contributes to the maintenance of genome stability and tumor suppression remains unknown. Here we report that Atf3-deficient (Atf3-/-) mice developed spontaneous tumors, and died significantly earlier than wild-type (Atf3+/+) mice. Consistent with these results, Atf3-/- mouse embryonic fibroblasts (MEFs) had more aberrant chromosomes and micronuclei, and were genetically unstable. Whereas we demonstrated that ATF3 activated p53 and promoted its pro-apoptotic activity in mouse thymi and small intestines, the chromosomal instability caused by Atf3 deficiency was largely dependent on the regulation of p53 by ATF3. Interestingly, loss of Atf3 also promoted spontaneous tumorigenesis in Trp53+/- mice, but did not affect tumor formation in Trp53-/- mice. Our results thus provide the first genetic evidence linking ATF3 to the suppression of the early development of cancer, and ...Continue Reading

  • References63
  • Citations1

Citations

Mentioned in this Paper

TP53 gene
Embryo
Atf3 protein, mouse
Study
ATF3 gene
Specimen Type - Fibroblasts
Apoptosis, Intrinsic Pathway
Micronuclei, Chromosome-Defective
Structure of Thymic Cortex
Genome

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

LRRK2 & Immunity During Infection

Mutations in the LRRK2 gene are a risk-factor for developing Parkinson’s disease. However, LRRK2 has been shown to function as a central regulator of vesicular trafficking, infection, immunity, and inflammation. Here is the latest research on the role of this kinase on immunity during infection.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Meningococcal Myelitis

Meningococcal myelitis is characterized by inflammation and myelin damage to the meninges and spinal cord. Discover the latest research on meningococcal myelitis here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.