The activator-recruited cofactor/Mediator coactivation subunit ARC92 is a functionally important target of the VP16 transcriptional activator

Fajun Yang, Rosalie DeBeaumont, Sharleen Zhou, Anders M. Näär

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The human activator-recruited cofactor (ARC), a family of large transcriptional coactivator complexes related to the yeast Mediator, was recently identified based on functional association with the activation domains of multiple cellular and viral transcriptional activators, including the herpes simplex viral activator VP16, sterol regulatory element binding protein, and NF-κB. Here we describe the biochemical purification and cloning of the 92-kDa ARC/Mediator subunit, ARC92, that is specifically targeted by the activation domain of the VP16 transactivator. Affinity chromatography using the VP16 activation domain followed by peptide microsequencing led to the identification of ARC92 as a specific cellular interaction partner of the VP16 activation domain. ARC92 associates with the VP16 activation domain in vitro and in vivo, and the VP16 binding domain of ARC92 is a strong competitive inhibitor of Gal4-VP16 in vivo. Moreover, small interfering RNA-mediated knockdown of ARC92 in human cells results in selective inhibition of Gal4-VP16 gene activation. Taken together, our results suggest that ARC92 is a direct and specific target of the VP16 transactivator that serves in the context of the ARC/Mediator coactivator as an important transducer of transcription activating signals from the VP16 activation domain to the RNA polymerase II transcriptional machinery.

Original languageEnglish (US)
Pages (from-to)2339-2344
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number8
DOIs
StatePublished - Feb 22 2004
Externally publishedYes

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Trans-Activators
Sterol Regulatory Element Binding Proteins
Herpes Simplex
RNA Polymerase II
Transducers
Affinity Chromatography
Small Interfering RNA
Transcriptional Activation
Organism Cloning
Yeasts
Gal-VP16
IgA receptor
In Vitro Techniques
Protein Domains

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The activator-recruited cofactor/Mediator coactivation subunit ARC92 is a functionally important target of the VP16 transcriptional activator. / Yang, Fajun; DeBeaumont, Rosalie; Zhou, Sharleen; Näär, Anders M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 8, 22.02.2004, p. 2339-2344.

Research output: Contribution to journalArticle

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