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

16Citations
Citations of this article
12Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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. © 2013 Macmillan Publishers Limited.

Author supplied keywords

Cite

CITATION STYLE

APA

Biswas, S., Shi, Q., Wernick, A., Aiello, A., & Zinkel, S. S. (2013). The loss of the BH3-only Bcl-2 family member Bid delays T-cell leukemogenesis in Atm-/-mice. Cell Death and Differentiation, 20(7), 869–877. https://doi.org/10.1038/cdd.2013.16

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free