[en] Myc oncoproteins are overexpressed in most cancers and are sufficient to accelerate cell proliferation and provoke transformation. However, in normal cells Myc also triggers apoptosis. All of the effects of Myc require its function as a transcription factor that dimerizes with Max. This complex induces genes containing CACGTG E-boxes, such as Ornithine decarboxylase (Odc), which harbors two of these elements. Here we report that in quiescent cells the Odc E-boxes are occupied by Max and Mnt, a putative Myc antagonist, and that this complex is displaced by Myc-Max complexes in proliferating cells. Knockdown of Mnt expression by stable retroviral RNA interference triggers many targets typical of the "Myc" response and provokes accelerated proliferation and apoptosis. Strikingly, these effects of Mnt knockdown are even manifest in cells lacking c-myc. Moreover, Mnt knockdown is sufficient to transform primary fibroblasts in conjunction with Ras. Therefore, Mnt behaves as a tumor suppressor. These findings support a model where Mnt represses Myc target genes and Myc functions as an oncogene by relieving Mnt-mediated repression.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nilsson, Jonas A; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
Maclean, Kirsteen H; Department of Biochemistry, St. Jude Children's Res. Hospital, Memphis, TN 38105, United States
Keller, Ulrich B; Department of Biochemistry, St. Jude Children's Res. Hospital, Memphis, TN 38105, United States
Pendeville-Samain, Hélène ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire ; Department of Biochemistry, St. Jude Children's Res. Hospital, Memphis, TN 38105, United States
Baudino, Troy A; Department of Biochemistry, St. Jude Children's Res. Hospital, Memphis, TN 38105, United States
Cleveland, John L; Department of Biochemistry, St. Jude Children's Res. Hospital, Memphis, TN 38105, United States ; St. Jude Children's Res. Hospital, Memphis, TN 38105, United States
Language :
English
Title :
Mnt loss triggers Myc transcription targets, proliferation, apoptosis, and transformation.
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