ArticleGenes & development2016
A gain-of-function senescence bypass screen identifies the homeobox transcription factor DLX2 as a regulator of ATM-p53 signaling.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- rs2357322 and rs17726078 Contribute to Breast Cancer Risk by Regulating DLX2 Expression.The breast journal · 2026Article
- A natural variation-based screen in mouse cells reveals USF2 as a regulator of the DNA damage response and cellular senescence.G3 (Bethesda, Md.) · 2023Article
- Article
- Lysosomal control of senescence and inflammation through cholesterol partitioning.Nature metabolism · 2023Article
- The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis.Cancers · 2021Review
- OB-Folds and Genome Maintenance: Targeting Protein-DNA Interactions for Cancer Therapy.Cancers · 2021Review
- Review
- Article
- XPO7 is a tumor suppressor regulating p21Genes & development · 2021Article
- Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer.International journal of molecular sciences · 2020Review
- The effects of Tel2 on cardiomyocyte survival.Life sciences · 2019Article
- Article
- Emerging roles of CST in maintaining genome stability and human disease.Frontiers in bioscience (Landmark edition) · 2018Review
- Fatty Acids, Antioxidants and Physical Activity in Brain Aging.Nutrients · 2017Review
- A triad of NRP2, DLX and p53 proteins in lung cancer metastasis.Oncotarget · 2017Article
- Coupling shRNA screens with single-cell RNA-seq identifies a dual role for mTOR in reprogramming-induced senescence.Genes & development · 2017Article
- p53-R273H upregulates neuropilin-2 to promote cell mobility and tumor metastasis.Cell death & disease · 2017Article
- A Chromatin-Focused siRNA Screen for Regulators of p53-Dependent Transcription.G3 (Bethesda, Md.) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Senescence stimuli activate multiple tumor suppressor pathways to initiate cycle arrest and a differentiation program characteristic of senescent cells. We performed a two-stage, gain-of-function screen to select for the genes whose enhanced expression can bypass replicative senescence. We uncovered multiple genes known to be involved in p53 and Rb regulation and ATM regulation, two components of the CST (CTC1-STN1-TEN1) complex involved in preventing telomere erosion, and genes such as REST and FOXO4 that have been implicated in aging. Among the new genes now implicated in senescence, we identified DLX2, a homeobox transcription factor that has been shown to be required for tumor growth and metastasis and is associated with poor cancer prognosis. Growth analysis showed that DLX2 expression led to increased cellular replicative life span. Our data suggest that DLX2 expression reduces the protein components of the TTI1/TTI2/TEL2 complex, a key complex required for the proper folding and stabilization of ATM and other members of the PIKK (phosphatidylinositol 3-kinase-related kinase) family kinase, leading to reduced ATM-p53 signaling and senescence bypass. We also found that the overexpression of DLX2 exhibited a mutually exclusive relationship with p53 alterations in cancer patients. Our functional screen identified novel players that may promote tumorigenesis by regulating the ATM-p53 pathway and senescence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.