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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2669-2677. Prepublished online as a Blood First Edition Paper on June 20, 2006; DOI 10.1182/blood-2006-02-005900. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-005900v1 108/8/2669    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dose, M. Articles by Gounari, F. Search for Related Content PubMed PubMed Citation Articles by Dose, M. Articles by Gounari, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2006 Accepted June 7, 2006 c-Myc mediates preTCR induced proliferation but not developmental progression Marei Dose, Irum Khan, Zhuyan Guo, Damian Kovalovsky, Andreas Krueger, Harald von Boehmer, Khashayarsha Khazaie, and Fotini Gounari* Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA, USA Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA * Corresponding author; email: fgounari{at}tufts-nemc.org. Constitutive and cell autonomous signals emanating from the preTCR promote proliferation, survival and differentiation of immature thymocytes. We show here that induction of preTCR signaling resulted in rapid elevation of c-Myc protein levels. Cre mediated thymocyte specific ablation of c-Myc in CD25+CD44- thymocytes reduced proliferation and cell growth at the preTCR checkpoint, resulting in thymic hypocellularity and a severe reduction in CD4+CD8+ thymocytes. In contrast, c-Myc deficiency did not inhibit preTCR mediated differentiation or survival. c-Myc-/- DN3 cells progressed to the DP stage and upregulated TCR surface expression in the absence of cell proliferation, in vivo as well as in vitro. These observations indicate that distinct signals downstream of the preTCR are responsible for proliferation versus differentiation, and demonstrate that c-Myc is only required for preTCR induced proliferation but is dispensable for developmental progression from the DN to the DP stage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Dose, B. P. Sleckman, J. Han, A. L. Bredemeyer, A. Bendelac, and F. Gounari Intrathymic proliferation wave essential for V{alpha}14+ natural killer T cell development depends on c-Myc PNAS, May 26, 2009; 106(21): 8641 - 8646. [Abstract] [Full Text] [PDF] M. P. Mycko, I. Ferrero, A. Wilson, W. Jiang, T. Bianchi, A. Trumpp, and H. R. MacDonald Selective Requirement for c-Myc at an Early Stage of V{alpha}14i NKT Cell Development J. Immunol., April 15, 2009; 182(8): 4641 - 4648. [Abstract] [Full Text] [PDF] J.-F. Brodeur, S. Li, M. d. S. Martins, L. Larose, and V. P. Dave Critical and Multiple Roles for the CD3{epsilon} Intracytoplasmic Tail in Double Negative to Double Positive Thymocyte Differentiation J. Immunol., April 15, 2009; 182(8): 4844 - 4853. [Abstract] [Full Text] [PDF] M. Rajasagi, M. Vitacolonna, B. Benjak, R. Marhaba, and M. Zoller CD44 promotes progenitor homing into the thymus and T cell maturation J. Leukoc. Biol., February 1, 2009; 85(2): 251 - 261. [Abstract] [Full Text] [PDF] T. Kreslavsky, A. I. Garbe, A. Krueger, and H. von Boehmer T cell receptor-instructed {alpha}{beta} versus {gamma}{delta} lineage commitment revealed by single-cell analysis J. Exp. Med., May 12, 2008; 205(5): 1173 - 1186. [Abstract] [Full Text] [PDF] C. Mao, E. G. Tili, M. Dose, M. C. Haks, S. E. Bear, I. Maroulakou, K. Horie, G. A. Gaitanaris, V. Fidanza, T. Ludwig, et al. Unequal Contribution of Akt Isoforms in the Double-Negative to Double-Positive Thymocyte Transition J. Immunol., May 1, 2007; 178(9): 5443 - 5453. [Abstract] [Full Text] [PDF]

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