Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death
Copyright policy )Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death
In yeast, activation of ATG1/ATG13 kinase complex initiates autophagy. This mechanism of autophagy initiation is conserved, as unc-51-like kinase 1 (ULK1) and unc-51-like kinase 2 (ULK2) are two mammalian functional homologues of ATG1 and form similar complex with mammalian ATG13. Here, we report that both ULK1 and ULK2 are transcriptional targets of tumor suppressor p53. In response to DNA damage, ULK1 and ULK2 are upregulated by p53. The upregulation of ULK1 (ULK2)/ATG13 complex by p53 is necessary for the sustained autophagy activity induced by DNA damage. In this context, elevated autophagy contributes to subsequent cell death. These findings suggest that ULK1 and ULK2 may mediate part of tumor suppression activity in mammalian cells and contribute to the efficacy of genotoxic chemotherapeutic drugs.
- National Institute of Biological Sciences, Beijing China (People's Republic of)
- The University of Texas Southwestern Medical Center United States
Original Paper, Cell Death, Intracellular Signaling Peptides and Proteins, Autophagy-Related Proteins, Electrophoretic Mobility Shift Assay, Protein Serine-Threonine Kinases, Polymerase Chain Reaction, Autophagy, Autophagy-Related Protein-1 Homolog, Humans, RNA Interference, Tumor Suppressor Protein p53, Adaptor Proteins, Signal Transducing, DNA Damage
Original Paper, Cell Death, Intracellular Signaling Peptides and Proteins, Autophagy-Related Proteins, Electrophoretic Mobility Shift Assay, Protein Serine-Threonine Kinases, Polymerase Chain Reaction, Autophagy, Autophagy-Related Protein-1 Homolog, Humans, RNA Interference, Tumor Suppressor Protein p53, Adaptor Proteins, Signal Transducing, DNA Damage
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).161 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!