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A conserved element in Myc that negatively regulates its proapoptotic activity
Author(s) -
Herbst Andreas,
Hemann Michael T,
Tworkowski Kathryn A,
Salghetti Simone E,
Lowe Scott W,
Tansey William P
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400333
Subject(s) - transcription factor , biology , psychological repression , proto oncogene proteins c myc , apoptosis , regulator , microbiology and biotechnology , conserved sequence , programmed cell death , transcription (linguistics) , cell growth , cancer research , genetics , gene , gene expression , peptide sequence , linguistics , philosophy
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.