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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hurlin, Peter J. Daniel, Colin J. Link, Jason M. Sears, Rosalie C. Zhou, Zi-qiang Ota, Sara |
| Description | Author Affiliation: Link JM ( Shriners Hospitals for Children-Portland, Portland, OR 97239, USA.); |
| Abstract | Mnt (Max's next tango) is a Max-interacting transcriptional repressor that can antagonize both the proproliferative and proapoptotic functions of Myc in vitro. To ascertain the physiologically relevant functions of Mnt and to help define the relationship between Mnt and Myc in vivo, we generated a series of mouse strains in which Mnt was deleted in T cells in the absence of endogenous c-Myc or in the presence of ectopic c-Myc. We found that apoptosis caused by loss of Mnt did not require Myc but that ectopic Myc expression dramatically decreased the survival of both Mnt-deficient T cells in vivo and Mnt-deficient MEFs in vitro. Consequently, Myc-driven proliferative expansion of T cells in vitro and thymoma formation in vivo were prevented by the absence of Mnt. Consistent with T-cell models, mouse embryo fibroblasts (MEFs) lacking Mnt were refractory to oncogenic transformation by Myc. Tumor suppression caused by loss of Mnt was linked to increased apoptosis mediated by reactive oxygen species (ROS). Thus, although theoretically and experimentally a Myc antagonist, the dominant physiological role of Mnt appears to be suppression of apoptosis. Our results redefine the physiological relationship between Mnt and Myc and requirements for Myc-driven oncogenesis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Physiology Cell Proliferation Cell Transformation, Neoplastic Proto-Oncogene Proteins C-myc Repressor Proteins T-Lymphocytes Cytology Animals Apoptosis Mice Reactive Oxygen Species Metabolism Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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