Progesterone Receptor Deficient in Chromatin Binding Has an Altered Cellular State

Jeannine Botos, Wenjuan Xian, David F. Smith, Catharine Smith

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Our previous work has shown that the progesterone receptor (PR) can exist in two distinct functional states in mammary adenocarcinoma cells. The differences in function included the ability to activate a promoter in organized chromatin, sensitivity to ligand, and ligand-independent activation. To determine whether these functional differences were because of altered cellular processing, we carried out biochemical analyses of the functionally distinct PRs. Although the majority of PR is localized to the nucleus, biochemical partitioning resulted in a loosely bound (cytosolic) fraction, and a tightly bound (nuclear) fraction. In the absence of progestins, the functionally distinct PRs differed significantly in partitioning between the two fractions. To characterize these fractions further, we analyzed interactions of unliganded PR with chaperones by coimmunoprecipitation. We determined that PR in the cytosolic fraction associated with hsp90 and p23. In contrast, PR in the nuclear fraction consisted of complexes containing hsp90, p23, and FKBP51 as well as PR that was dimerized and highly phosphorylated. Hormone treatment significantly reduced the formation of all PR-chaperone complexes. The hsp90 inhibitor, geldanamycin, similarly blocked transcriptional activity of both functionally distinct receptors. However, the two forms of the PR differed in their ability to associate with the mouse mammary tumor virus promoter in organized chromatin. These findings provide new information about the composition and distribution of mature progesterone receptor complexes in mammary adenocarcinoma cells, and suggest that differences in receptor subcellular distribution have a significant impact on their function. These findings also reveal that transiently expressed steroid receptors may not always be processed like their endogenous counterparts.

Original languageEnglish (US)
Pages (from-to)15231-15239
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number15
DOIs
StatePublished - Apr 9 2004
Externally publishedYes

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Progesterone Receptors
Chromatin
Adenocarcinoma
Breast
Ligands
Mouse mammary tumor virus
Steroid Receptors
Progestins
Viruses
Carcinogens
Tumors
Chemical activation
Hormones
Processing
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Progesterone Receptor Deficient in Chromatin Binding Has an Altered Cellular State. / Botos, Jeannine; Xian, Wenjuan; Smith, David F.; Smith, Catharine.

In: Journal of Biological Chemistry, Vol. 279, No. 15, 09.04.2004, p. 15231-15239.

Research output: Contribution to journalArticle

Botos, Jeannine ; Xian, Wenjuan ; Smith, David F. ; Smith, Catharine. / Progesterone Receptor Deficient in Chromatin Binding Has an Altered Cellular State. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 15. pp. 15231-15239.
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