RGD Reference Report - The Myc transactivation domain promotes global phosphorylation of the RNA polymerase II carboxy-terminal domain independently of direct DNA binding. - Rat Genome Database

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Pathways

The Myc transactivation domain promotes global phosphorylation of the RNA polymerase II carboxy-terminal domain independently of direct DNA binding.

Authors: Cowling, VH  Cole, MD 
Citation: Cowling VH and Cole MD, Mol Cell Biol. 2007 Mar;27(6):2059-73. Epub 2007 Jan 22.
RGD ID: 9681447
Pubmed: PMID:17242204   (View Abstract at PubMed)
PMCID: PMC1820498   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.01828-06   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gtf2h1Ratchromatin binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gtf2h1  (general transcription factor IIH subunit 1)


Additional Information