An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II

TY - JOUR

T1 - An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II

AU - Cowling, V. H.

AU - Cole, M. D.

N1 - MEDLINE® is the source for the MeSH terms of this document.

PY - 2008/2/21

Y1 - 2008/2/21

N2 - Myc promotes both normal cell proliferation and oncogenic transformation through the activation and repression of target genes. The c-Myc-S protein is a truncated form of c-Myc that is produced in some cells from translation initiation at an internal AUG codon. We report that c-Myc-S and a similar truncated form of N-MycWT can fully rescue the proliferation defect in myc-null fibroblasts, but rescue is dependent on the highly conserved Myc homology box II (MBII). Global gene expression studies show that the N-Myc equivalent of c-Myc-S is defective for virtually all transcriptional activation of Myc target genes but remains active for the majority of transcriptional repression. Repression by Myc-S is dependent on MBII, but it does not bind to several known nuclear cofactors. These data suggest that repression by Myc involves recruitment of a novel MBII-dependent cofactor.

AB - Myc promotes both normal cell proliferation and oncogenic transformation through the activation and repression of target genes. The c-Myc-S protein is a truncated form of c-Myc that is produced in some cells from translation initiation at an internal AUG codon. We report that c-Myc-S and a similar truncated form of N-MycWT can fully rescue the proliferation defect in myc-null fibroblasts, but rescue is dependent on the highly conserved Myc homology box II (MBII). Global gene expression studies show that the N-Myc equivalent of c-Myc-S is defective for virtually all transcriptional activation of Myc target genes but remains active for the majority of transcriptional repression. Repression by Myc-S is dependent on MBII, but it does not bind to several known nuclear cofactors. These data suggest that repression by Myc involves recruitment of a novel MBII-dependent cofactor.

KW - c-Myc-S

KW - Myc

KW - Transcriptional repression

KW - Transactivation

KW - Cell proliferation

UR - https://www.scopus.com/pages/publications/39749144542

U2 - 10.1038/sj.onc.1210734

DO - 10.1038/sj.onc.1210734

M3 - Article

AN - SCOPUS:39749144542

SN - 0950-9232

VL - 27

SP - 1327

EP - 1332

JO - Oncogene

JF - Oncogene

IS - 9

ER -