Ligands have various potential effects on the degradation of pregnane X receptor by proteasome

Hisashi Masuyama, Hideshi Inoshita, Yuji Hiramatsu, Takafumi Kudo

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The degradations of several nuclear receptors are involved in the proteasome-mediated pathway. In our recent experiments, we found that mouse pregnane X receptor (PXR) interacted with suppressor for gal1 (SUG1), a component of the proteasome, in a progesterone-dependent manner, but that endocrine-disrupting chemicals (EDCs), phthalic acid and nonylphenol, which activated PXR-mediated transcription, did not enhance this interaction. PXR protein levels were markedly increased in the presence of proteasome inhibitors, suggesting that PXR may be degraded by proteasome. Furthermore, in the absence of ongoing protein synthesis, there is much slower degradation of PXR in the presence ofphthalic acid compared with that in the presence of progesterone. The transient expression studies demonstrated that overexpression of wild-type SUG1 generated proteolytic PXR fragments, and these productions were blocked by a proteasome inhibitor. Functionally, expression of SUG1 inhibited PXR- and progesterone-mediated transcription. Moreover, in the presence of EDCs, SUG1 had no effect on the transcription. These findings indicate that the interaction between PXR and SUG1 may be involved in the proteasome-mediated degradation. Moreover, an EDC strongly blocks the degradation of PXR compared with progesterone, suggesting that EDCs may affect PXR-mediated transcription of target genes through upregulation of the PXR protein level.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalEndocrinology
Volume143
Issue number1
DOIs
Publication statusPublished - 2002

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Proteasome Endopeptidase Complex
Ligands
Endocrine Disruptors
Progesterone
Proteasome Inhibitors
pregnane X receptor
Proteins
Cytoplasmic and Nuclear Receptors
Up-Regulation
Acids

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Ligands have various potential effects on the degradation of pregnane X receptor by proteasome. / Masuyama, Hisashi; Inoshita, Hideshi; Hiramatsu, Yuji; Kudo, Takafumi.

In: Endocrinology, Vol. 143, No. 1, 2002, p. 55-61.

Research output: Contribution to journalArticle

Masuyama, Hisashi ; Inoshita, Hideshi ; Hiramatsu, Yuji ; Kudo, Takafumi. / Ligands have various potential effects on the degradation of pregnane X receptor by proteasome. In: Endocrinology. 2002 ; Vol. 143, No. 1. pp. 55-61.
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