Specific ubiquitin-conjugating enzymes promote degradation of specific nuclear receptor coactivators

Feng Yan, Xiuhua Gao, David M. Lonard, Zafar Nawaz

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Nuclear receptor coactivators (NRCoAs) are nuclear hormone receptor-associated regulatory proteins that interact with members of the nuclear receptor superfamily in the presence of their cognate ligand, enhancing their transcriptional activity. The identification of ubiquitin-proteasome pathway proteins as coactivators provides evidence that ubiquitin-proteasome-mediated protein degradation plays an integral role in eukaryotic gene transcription. It has also been observed that nuclear receptors themselves are ubiquitinated and degraded in a hormone-dependent manner and that ubiquitin-proteasome function is essential for most nuclear receptors to function as transactivators. Here, we show that specific ubiquitin-proteasome pathway enzymes target specific NRCoA proteins in vivo and in vitro. First, using a temperature-sensitive cell line that contains a thermolabile ubiquitin-activating E1 enzyme, we confirmed that NRCoA proteins are targets of the ubiquitin-proteasome pathway. Then using coimmunoprecipitation studies, we also demonstrate that in vivo, NRCoA proteins are ubiquitinated. Finally, we illustrate that in vitro, NRCoA ubiquitination and degradation depend on the ubiquitin-activating enzyme (E1) and on specific ubiquitin-conjugating enzymes (E2) for each of the coactivators.

Original languageEnglish
Pages (from-to)1315-1331
Number of pages17
JournalMolecular Endocrinology
Volume17
Issue number7
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

Nuclear Receptor Coactivators
Ubiquitin-Conjugating Enzymes
Proteasome Endopeptidase Complex
Ubiquitin
Cytoplasmic and Nuclear Receptors
Ubiquitin-Activating Enzymes
Proteins
Ubiquitinated Proteins
Trans-Activators
Ubiquitination
Proteolysis
Hormones
Ligands
Cell Line
Temperature
Enzymes
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Specific ubiquitin-conjugating enzymes promote degradation of specific nuclear receptor coactivators. / Yan, Feng; Gao, Xiuhua; Lonard, David M.; Nawaz, Zafar.

In: Molecular Endocrinology, Vol. 17, No. 7, 01.07.2003, p. 1315-1331.

Research output: Contribution to journalArticle

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