MNT and Emerging Concepts of MNT-MYC Antagonism
نویسندگان
چکیده
MYC family proteins play fundamental roles in stem and progenitor cell homeostasis, morphogenesis and cancer. As expected for proteins that profoundly affect the fate of cells, the activities of MYC are regulated at a multitude of levels. One mechanism with the potential to broadly affect the activities of MYC is transcriptional antagonism by a group of MYC-related transcriptional repressors. From this group, the protein MNT has emerged as having perhaps the most far-reaching impact on MYC activities. In this review, we discuss the current understanding of MNT, its regulation and how, as a MYC antagonist, it functions both as a tumor suppressor and facilitator of MYC-driven proliferation and oncogenesis.
منابع مشابه
Mnt–Max to Myc–Max complex switching regulates cell cycle entry
The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and is an important regulator of cell cycle entry. In contrast to c-Myc, the putative Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt and Myc require interaction with Max for specific DNA binding at E-box sites, but have opposing transcriptional activities. Here, we show that c-Myc in...
متن کاملA critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis.
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 ...
متن کاملMnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression.
The proto-oncogene c-Myc plays a central role in cell growth and the development of human tumors. c-Myc interacts with Max and Myc-Max complexes bind to E-box and related sequences to activate transcription. Max also interacts with Mnt but Mnt-Max complexes repress transcription when bound to these sequences. MNT maps to human chromosome 17p13.3, a region frequently deleted in various human tum...
متن کاملMYC needs MNT
MYC family members c-MYC, N-MYC and L-MYC are amplified, translocated and otherwise deregulated in numerous and diverse tumor types. These events, which typically lead to constitutively increased MYC, provide a proliferative advantage to cells by boosting anabolic metabolism and supporting cell cycle progression. However, the proliferative response to excessive MYC is countered in many cell typ...
متن کاملMnt loss triggers Myc transcription targets, proliferation, apoptosis, and transformation.
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 ...
متن کامل