Regulation of nuclear receptor transcriptional activity by a novel DEAD box RNA helicase (DP97)

Ramji R. Rajendran, Anne C. Nye, Jonna Frasor, Rashna D. Balsara, Paolo G.V. Martini, Benita S. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

We have identified a novel DEAD box RNA helicase (97 kDa, DP97) from a breast cancer cDNA library that interacts in a hormone-dependent manner with nuclear receptors and represses their transcriptional activity. DP97 has RNA-dependent ATPase activity, and mapping studies localize the interacting regions of DP97 and nuclear receptors to the C-terminal region of DP97 and the hormone binding/activation function-2 region of estrogen receptors (ER), as well as several other nuclear receptors. Repression by DP97 maps to a small region (amino acids 589-631) that has homology to a repression domain in the corepressor protein NCoR2/SMRTe. This region of DP97 is necessary and sufficient for its intrinsic repression activity. The N-terminal helicase region of DP97 is, however, dispensable for its transcriptional repressor activity. The knockdown of endogenous cellular DP97 by antisense DP97 or RNA interference (siRNA for DP97) results in significant enhancement of the expression of estradiol-ER-stimulated genes and attenuation of the repression of genes inhibited by the estradiol-ER. This implies that endogenous DP97 normally dampens stimulation and intensifies repression of estra-diol-ER-regulated genes. Our findings add to the growing evidence that RNA helicases can associate with nuclear receptors and function as coregulators to modulate receptor transcriptional activity.

Original languageEnglish (US)
Pages (from-to)4628-4638
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number7
DOIs
StatePublished - Feb 14 2003

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DEAD-box RNA Helicases
Cytoplasmic and Nuclear Receptors
Estrogen Receptors
Estradiol Receptors
Genes
Estradiol
Hormones
RNA Helicases
Co-Repressor Proteins
RNA Interference
Gene Library
Small Interfering RNA
Chemical activation
RNA
Breast Neoplasms
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Regulation of nuclear receptor transcriptional activity by a novel DEAD box RNA helicase (DP97). / Rajendran, Ramji R.; Nye, Anne C.; Frasor, Jonna; Balsara, Rashna D.; Martini, Paolo G.V.; Katzenellenbogen, Benita S.

In: Journal of Biological Chemistry, Vol. 278, No. 7, 14.02.2003, p. 4628-4638.

Research output: Contribution to journalArticle

Rajendran, Ramji R. ; Nye, Anne C. ; Frasor, Jonna ; Balsara, Rashna D. ; Martini, Paolo G.V. ; Katzenellenbogen, Benita S. / Regulation of nuclear receptor transcriptional activity by a novel DEAD box RNA helicase (DP97). In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 7. pp. 4628-4638.
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