Journal article
A Myc-dependent division timer complements a cell-death timer to regulate T cell and B cell responses
S Heinzel, T Binh Giang, A Kan, JM Marchingo, BK Lye, LM Corcoran, PD Hodgkin
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/ni.3598
Abstract
T lymphocytes and B lymphocytes integrate activating signals to control the size of their proliferative response. Here we report that such control was achieved by timed changes in the production rate of cell-cycle-regulating proto-oncoprotein Myc, with division cessation occurring when Myc levels fell below a critical threshold. The changing pattern of the level of Myc was not affected by cell division, which identified the regulating mechanism as a cell-intrinsic, heritable temporal controller. Overexpression of Myc in stimulated T cells and B cells did not sustain cell proliferation indefinitely, as a separate 'time-to-die' mechanism, also heritable, was programmed after lymphocyte activat..
View full abstractGrants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank S. Cory (The Walter and Eliza Hall Institute) for vav-myc10 mice; P. Bouillet (The Walter and Eliza Hall Institute) for Bcl-2-Tg, Bcl2l11<SUP>-/-</SUP> and E mu-Myc mice; M. Hancock and T. Kratina for technical assistance; J. Zhou for help in figure preparation; and S. Cory, M. Dowling, K. Duffy and A. Strasser for critical review of the manuscript. Supported by the National Health and Medical Research Council of Australia (Project Grants 1010654 and 1057831 and Program Grant 1054925; and fellowships to P.D.H. and L.M.C.), Victorian State Government Operational Infrastructure Support, an Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme (361646), The Australian Department of Education and Training (Australian Postgraduate Award to J.M.M.), The Walter and Eliza Hall Institute (Edith Moffat Scholarship to J.M.M.), the Cancer Council of Victoria (Sydney Parker Smith Postdoctoral Research Fellowship to J.M.M.) and The University of Melbourne (Melbourne International Research Scholarship for B.K.L. and Melbourne International Fee Remission Scholarship for B.K.L.).