Abstract
The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein. PML is involved in multiple apoptotic pathways and is thought to be pivotal in gamma irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation. In addition, gamma irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates gamma irradiation-induced apoptosis in a p53-independent manner through an ataxia telangiectasia-mutated (ATM)-hCds1/Chk2-PML pathway. Our results provide the first evidence of a functional relationship between PML and a checkpoint kinase in gamma irradiation-induced apoptosis.
MeSH terms
-
Adenoviridae / genetics
-
Apoptosis*
-
Ataxia Telangiectasia Mutated Proteins
-
Cell Cycle Proteins
-
Cell Nucleus / metabolism
-
Checkpoint Kinase 2
-
DNA Damage
-
DNA-Binding Proteins
-
Dose-Response Relationship, Radiation
-
Electroporation
-
Gamma Rays
-
Glutathione Transferase / metabolism
-
HeLa Cells
-
Humans
-
Microscopy, Confocal
-
Neoplasm Proteins / metabolism
-
Neoplasm Proteins / physiology*
-
Nuclear Proteins*
-
Phosphorylation
-
Plasmids / metabolism
-
Precipitin Tests
-
Promyelocytic Leukemia Protein
-
Protein Serine-Threonine Kinases / metabolism
-
Protein Serine-Threonine Kinases / physiology*
-
Protein Transport
-
Recombinant Fusion Proteins / metabolism
-
Serine / chemistry
-
Time Factors
-
Transcription Factors / metabolism
-
Transcription Factors / physiology*
-
Transfection
-
Tumor Suppressor Protein p53 / metabolism
-
Tumor Suppressor Proteins
-
U937 Cells
Substances
-
Cell Cycle Proteins
-
DNA-Binding Proteins
-
Neoplasm Proteins
-
Nuclear Proteins
-
Promyelocytic Leukemia Protein
-
Recombinant Fusion Proteins
-
Transcription Factors
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
PML protein, human
-
Serine
-
Glutathione Transferase
-
Checkpoint Kinase 2
-
ATM protein, human
-
Ataxia Telangiectasia Mutated Proteins
-
CHEK2 protein, human
-
Protein Serine-Threonine Kinases