Journal article
RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice
ARD Delbridge, SHM Pang, CJ Vandenberg, S Grabow, BJ Aubrey, L Tai, MJ Herold, A Strasser
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2016
DOI: 10.1084/jem.20150477
Abstract
Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53-/- mice. Thus, potentially oncogenic DNA l..
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Awarded by National Science Foundation
Funding Acknowledgements
This work was supported by grants and fellowships from the Cancer Council of Victoria (S. Grabow and A.R.D. Delbridge [Sydney Parker Smith Postdoctoral Research Fellowship]), Leukemia Foundation National Research Program Clinical PhD Scholarship (B.J. Aubrey), Lady Tata Postdoctoral Fellowship (S. Grabow), the National Health and Medical Research Council (Program grant #1016701; SPRF Fellowship 1020363, A. Strasser; Project Grant #APP1049720, M.J. Herold), the Leukemia and Lymphoma Society (SCOR grant #7001-13), the estate of Anthony (Toni) Redstone OAM, Melbourne International Research Scholarship (University of Melbourne, S. Grabow), Melbourne International Fee Remission Scholarship (University of Melbourne, S. Grabow), Australian Postgraduate Award (A.R.D. Delbridge), Cancer Therapeutics CRC Top-up Scholarship (S. Grabow and ARDD), and the Ian Potter Foundation. This work was made possible by operational infrastructure grants through the Australian Government Independent Medical Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support Program.