ATM-dependent phosphorylation of heterogeneous nuclear ribonucleoprotein K promotes p53 transcriptional activation in response to DNA damage.
Previous work has established that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is stabilized in an ATM-dependent manner in response to DNA damage and acts as a cofactor for p53-mediated transcription. Here, we show that in response to DNA damage caused by ionizing radiation, hnRNP K is phosphorylated in an ATM-dependent manner. Furthermore, our data indicate that ATM-dependent hnRNP K phosphorylation is required for its stabilization and its function as a p53 transcriptional cofactor in response to DNA damage. These findings thereby establish hnRNP K as an ATM target and help define how ATM orchestrates p53-dependent transcriptional responses in response to genotoxic stress.
DNA Damage Response Group, Basic Medical Science Department, St. George's University of London, London, UK.
Abdeladim
A
Moumen
Christine
C
Magill
Katherine L
KL
Dry
Stephen P
SP
Jackson
D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005720:Gamma Rays; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D014158:Transcription, Genetic / Q000528:radiation effects; D015533:Transcriptional Activation / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases
ATM; DNA damage; p53; phosphorylation; transcription