Affiliation:
1. Departments of Pharmacology and Genetics, Dartmouth Medical School, One Medical Center Drive, Lebanon, New Hampshire 03756
Abstract
ABSTRACT
Myc
is a transcription factor which is dependent on its DNA binding domain
for transcriptional regulation of target genes. Here, we report the
surprising finding that Myc mutants devoid of direct DNA binding
activity and Myc target gene regulation can rescue a substantial
fraction of the growth defect in
myc
−/−
fibroblasts. Expression of the Myc transactivation domain alone induces
a transcription-independent elevation of the RNA polymerase II (Pol II)
C-terminal domain (CTD) kinases cyclin-dependent kinase 7 (CDK7) and
CDK9 and a global increase in CTD phosphorylation. The Myc
transactivation domain binds to the transcription initiation sites of
these promoters and stimulates TFIIH binding in an MBII-dependent
manner. Expression of the Myc transactivation domain increases CDK mRNA
cap methylation, polysome loading, and the rate of
translation. We find that some traditional Myc
transcriptional target genes are also regulated by this Myc-driven
translation mechanism. We propose that Myc transactivation
domain-driven RNA Pol II CTD phosphorylation has broad effects on both
transcription and mRNA
metabolism.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
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