TITLE

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

AUTHOR(S)
Biswas, S; Shi, Q; Wernick, A; Aiello, A; Zinkel, S S
PUB. DATE
July 2013
SOURCE
Cell Death & Differentiation;Jul2013, Vol. 20 Issue 7, p869
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
88057100

 

Related Articles

  • p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision. Bouafia, Amine; Corre, Sébastien; Gilot, David; Mouchet, Nicolas; Prince, Sharon; Galibert, Marie-Dominique // PLoS Genetics;May2014, Vol. 10 Issue 5, p1 

    Genomic instability is a major hallmark of cancer. To maintain genomic integrity, cells are equipped with dedicated sensors to monitor DNA repair or to force damaged cells into death programs. The tumor suppressor p53 is central in this process. Here, we report that the ubiquitous transcription...

  • FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. Castella, Maria; Jacquemont, Celine; Thompson, Elizabeth L.; Yeo, Jung Eun; Cheung, Ronald S.; Huang, Jen-Wei; Sobeck, Alexandra; Hendrickson, Eric A.; Taniguchi, Toshiyasu // PLoS Genetics;10/2/2015, Vol. 11 Issue 10, p1 

    The Fanconi anemia (FA)-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex). However, the regulation...

  • TLK1B mediated phosphorylation of Rad9 regulates its nuclear/cytoplasmic localization and cell cycle checkpoint. Awate, Sanket; De Benedetti, Arrigo // BMC Molecular Biology;2/9/2016, Vol. 17, p1 

    Background: The Tousled like kinase 1B (TLK1B) is critical for DNA repair and survival of cells. Upon DNA damage, Chk1 phosphorylates TLK1B at S457 leading to its transient inhibition. Once TLK1B regains its kinase activity it phosphorylates Rad9 at S328. In this work we investigated the...

  • Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in cancer. Pihan, German A. // Frontiers in Oncology;Nov2013, Vol. 3, p1 

    The unique ability of centrosomes to nucleate and organize microtubules makes them unrivaled conductors of important interphase processes, such as intracellular payload traffic, cell polarity, cell locomotion, and organization of the immunologic synapse. But it is in mitosis that centrosomes...

  • Reduced Phosphorylation of Histone Variant H2Ax in the Organ of Corti is Associated with Otoprotection from Noise Injury. Guthrie, O'neil W.; Xu, Helen // Otolaryngology: Current Research;Special Issue2012, Vol. 2 Issue S, Special section p1 

    Research on the molecular bases of noise induced hearing loss has revealed that noise exposure produces multiple independent and complementary biochemical cascades that could damage DNA. The phosphorylation of Ser139 of histone variant H2Ax (γ-H2Ax) occurs within one minute following DNA...

  • Comparative Study of Radioresistance between Feline Cells and Human Cells. Yoshihiro Fujii; Yurkon, Charles R.; Junko Maeda; Genet, Stefan C.; Nobuo Kubota; Akira Fujimori; Takashi Mori; Kohji Maruo; Takamitsu A. Kato // Radiation Research;Jul2013, Vol. 180 Issue 1, p70 

    Radioresistance of cats has been seen in animal radiotherapy. Feline radioresistance and its underlying mechanism(s) were investigated in fibroblast cells and lymphocytes. We hypothesized that radioresistance was attributable to an increase in the cells ability to repair DNA damage. To...

  • Increased Mutagenic Joining of Enzymatically-Induced DNA Double-Strand Breaks in High-Charge and Energy Particle Irradiated Human Cells. Zhentian Li; Hudson, Farlyn Z.; Huichen Wang; Ya Wang; Zhuan Bian; Murnane, John P.; Dynan, William S. // Radiation Research;Jul2013, Vol. 180 Issue 1, p17 

    The carcinogenic risk of high-charge and energy (HZE) particle exposure arises from its ability to both induce complex DNA damage and from its ability to evoke deleterious, non-DNA targeted effects. We investigate here whether these nontargeted effects involve dysregulation of double-strand...

  • Histone Modifications and DNA Double-Strand Break Repair after Exposure to Ionizing Radiations. Hunt, Clayton R.; Ramnarain, Deepti; Horikoshi, Nobuo; Iyengar, Puneeth; Pandita, Raj K.; Shay, Jerry W.; Pandita, Tej K. // Radiation Research;Apr2013, Vol. 179 Issue 4, p383 

    Ionizing radiation exposure induces highly lethal DNA double-strand breaks (DSBs) in all phases of the cell cycle. After DSBs are detected by the cellular machinery, these breaks are repaired by either of two mechanisms: (1) nonhomologous end joining (NHEJ), which re-ligates the broken ends of...

  • DNA repair: A single-edged sword? Burgess, Darren J. // Nature Reviews Cancer;Jan2011, Vol. 11 Issue 1, p7 

    The article highlights two research papers on DNA repair mechanisms. It reveals that repression of translesion synthesis (TLS) can sensitize chemoresistant tumours to therapy. It says that TLS is a DNA damage tolerance mechanism in which substitute DNA polymerases utilize DNA synthesis to...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics