Proapoptotic BID is an ATM effector in the DNA-damage response.

The "BH3-only" proapoptotic BCL-2 family members are sentinels of intracellular damage. Here, we demonstrated that the BH3-only BID protein partially localizes to the nucleus in healthy cells, is important for apoptosis induced by DNA damage, and is phosphorylated following induction of double-strand breaks in DNA. We also found that BID ...
phosphorylation is mediated by the ATM kinase and occurs in mouse BID on two ATM consensus sites. Interestingly, BID-/- cells failed to accumulate in the S phase of the cell cycle following treatment with the topoisomerase II poison etoposide; reintroducing wild-type BID restored accumulation. In contrast, introducing a nonphosphorylatable BID mutant did not restore accumulation in the S phase and resulted in an increase in cellular sensitivity to etoposide-induced apoptosis. These results implicate BID as an ATM effector and raise the possibility that proapoptotic BID may also play a prosurvival role important for S phase arrest.
Mesh Terms:
Animals, Apoptosis, BH3 Interacting Domain Death Agonist Protein, Binding Sites, Carrier Proteins, Cell Cycle Proteins, Cell Nucleus, Cell Survival, Cells, Cultured, DNA, DNA Damage, DNA Topoisomerases, Type II, DNA-Binding Proteins, Etoposide, Fibroblasts, Genes, cdc, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Nucleic Acid Synthesis Inhibitors, Phosphorylation, Protein-Serine-Threonine Kinases, S Phase, Topoisomerase II Inhibitors, Tumor Suppressor Proteins
Cell
Date: Aug. 26, 2005
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