A conserved element in Myc that negatively regulates its proapoptotic activity
Open Access
- 1 February 2005
- journal article
- Published by Springer Nature in EMBO Reports
- Vol. 6 (2) , 177-183
- https://doi.org/10.1038/sj.embor.7400333
Abstract
Myc is an oncoprotein transcription factor that promotes cell proliferation and apoptosis. Analysis of highly conserved elements within vertebrate Myc proteins has been instrumental in defining the functions of the Myc protein. Here, we probe the role of a highly conserved, but little studied, element within the central region of c‐Myc, termed ‘Myc box III’ (MbIII). We show that MbIII is important for transcriptional repression by Myc, and for transformation both in vitro and in a mouse model of lymphomagenesis. Curiously, disruption of MbIII decreases transformation activity by increasing the efficiency with which Myc can induce apoptosis, suggesting that MbIII is a negative regulator of programmed cell death. These findings reveal a role for MbIII in Myc biology, and establish that the oncogenic capacity of Myc is linked directly to its ability to temper the apoptotic response.Keywords
This publication has 20 references indexed in Scilit:
- Erratum: Multiple cell-type-specific elements regulate Myc protein stabilityOncogene, 2004
- Multiple cell-type-specific elements regulate Myc protein stabilityOncogene, 2004
- Skp2 Regulates Myc Protein Stability and ActivityMolecular Cell, 2003
- c-MYC: more than just a matter of life and deathNature Reviews Cancer, 2002
- Spontaneous Reversion of tsBN67 Cell Proliferation and Cytokinesis Defects in the Absence of HCF-1 FunctionExperimental Cell Research, 2002
- A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer TherapyCell, 2002
- Induction of apoptosis in fibroblasts by c-myc proteinCell, 1992
- Chimaeras of Myc oncoprotein and steroid receptors cause hormone-dependent transformation of cellsNature, 1989
- Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cellsNature, 1988
- Evolutionarily conserved regions of the human c-myc protein can be uncoupled from transforming activity.Proceedings of the National Academy of Sciences, 1987