Ligand-free RAR can interact with the RNA polymerase II subunit hsRPB7 and repress transcription

Xi Qiang Shen, Athanasios Bubulya, Xiao Feng Zhou, Vladimir Khazak, Erica A. Golemis, Lirim Shemshedini

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Upon binding retinoic acid (RA), the retinoic acid receptors (RARs) are able to positively and negatively regulate transcription. It has been shown that the DNA-binding domain and carboxy terminus of RARs are necessary for the ligand-dependent ability of the receptor to repress AP-1 transcriptional activity. A fusion of these two regions, shown to constitutively inhibit AP-1 activity, was used in a yeast two-hybrid screen to identify a novel hRARα- interacting protein. This protein, hsRPB7, a subunit of RNA polymerase II, interacts with hRARα in the absence of RA and addition of RA disrupts the interaction. Truncation analysis indicates that hsRPB7 specifically interacts with the hRARα DNA-binding domain. This interaction appears to compromise transcription, since overexpressed hRARα, in the absence of RA, is able to repress the activity of several RNA polymerase II-dependent activators, including AP-1 and the glucocorticoid receptor. This repression is relieved by transfected hsRPB7, strongly suggesting that ligand-free hRARα can block AP-1 activity by sequestering hsRPB7. The repression is dependent on the integrity of the hRARα DBD, since a mutation within the DBD blocks both the hRARα-hsRPB7 interaction and ligand-free hRARα repression of AP-1. These results provide evidence that non-liganded hRARα can regulate transcription by directly interacting with RNA polymerase II, and thus suggest a novel pathway by which hRARα can cross-talk with AP-1 and perhaps other families of transcriptional activators.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalEndocrine
Volume10
Issue number3
DOIs
StatePublished - 1999

Keywords

  • AP-1
  • Nuclear receptors
  • RAR
  • RNA polymerase II
  • Transcription
  • hsRPB7

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