The loss of the BH3-only Bcl-2 family member Bid delays T-cell leukemogenesis in Atm-/- mice.

Biswas S, Shi Q, Wernick A, Aiello A, Zinkel SS
Cell Death Differ. 2013 20 (7): 869-77

PMID: 23470523 · PMCID: PMC3679453 · DOI:10.1038/cdd.2013.16

Multicellular organisms maintain genomic integrity and resist tumorigenesis through a tightly regulated DNA damage response (DDR) that prevents propagation of deleterious mutations either through DNA repair or programmed cell death. An impaired DDR leads to tumorigenesis that is accelerated when programmed cell death is prevented. Loss of the ATM (ataxia telangiectasia mutated)-mediated DDR in mice results in T-cell leukemia driven by accumulation of DNA damage accrued during normal T-cell development. Pro-apoptotic BH3-only Bid is a substrate of Atm, and Bid phosphorylation is required for proper cell cycle checkpoint control and regulation of hematopoietic function. In this report, we demonstrate that, surprisingly, loss of Bid increases the latency of leukemogenesis in Atm-/- mice. Bid-/-Atm-/- mice display impaired checkpoint control and increased cell death of DN3 thymocytes. Loss of Bid thus inhibits T-cell tumorigenesis by increasing clearance of damaged cells, and preventing propagation of deleterious mutations.

MeSH Terms (22)

Animals Annexin A5 Apoptosis Ataxia Telangiectasia Mutated Proteins BH3 Interacting Domain Death Agonist Protein Cell Cycle Proteins Checkpoint Kinase 1 Chromosomal Proteins, Non-Histone Disease Models, Animal DNA-Binding Proteins DNA Damage Female Leukemia, T-Cell Male Mice Mice, Knockout Protein-Serine-Threonine Kinases Protein Kinases T-Lymphocytes Thymocytes Tumor Suppressor p53-Binding Protein 1 Tumor Suppressor Proteins

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