Development of a monoclonal antibody to the rabbit 8.5S uterine progestin receptor

Nakao, Kazuso; Myers, John E.; Faber, Lee E.

doi:10.1139/o85-005

Cited by 54 publications

(21 citation statements)

References 2 publications

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“…The anti-FAP48 polyclonal antibody (pAb) 766 was generated from a peptide localized at the COOH-terminal part of the coding sequence of human FAP48 (amino acids 400-417) and encompassed six amino acids common for the two isoforms FAP48͞FAP68. Anti-FKBP52 mAb EC1 and anti-FKBP52 pAB173 were described (12,23). Anti-6-His mAb was from CLONTECH, anti-FKBP12 pAb was from Affinity Bioreagents (Golden, CO), anticalcineurin͞PP2B␤ was from Upstate Biotechnology (Lake Placid, NY), anti-ACTIVE p38 pAb and anti-ACTIVE JNK pAb were both from Promega, anti-ASS mAb and anti-Mxi1 mAb were both from Becton Dickinson, anti-HSP70 was from StressGen Biotechnologies (Victoria, BC, Canada), and anti-NFAT pAb 67.1 was generously provided by A. Rao (Harvard Medical School, Boston).…”

Section: Methodsmentioning

confidence: 99%

The FKBP-associated protein FAP48 is an antiproliferative molecule and a player in T cell activation that increases IL2 synthesis

Krummrei

Baulieu

Chambraud

2003

Proc. Natl. Acad. Sci. U.S.A.

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FAP48 was identified and cloned thanks to its interaction with FK506-binding proteins (FKBPs) such as FKBP52 and FKBP12, which belong to the large family of immunophilins that bind the macrolide immunosuppressant drugs FK506 and rapamycin. We have previously shown that FAP48 -FKBP complexes are dissociated by FK506 and rapamycin, suggesting that FAP48 is an endogenous ligand of FKBP. The present work describes the biochemical consequences of FAP48 overexpression, induced by the tetracycline analogue doxycycline, in an established cell line derived from Jurkat T cells. We report that overexpression of FAP48 results in the inhibition of cellular proliferation as does the exposure of Jurkat T cells to FK506. We also show that the expression levels of argininosuccinate synthetase and the Myc antagonist Mxi1 are modified by overexpression of FAP48, suggesting that these proteins could be good candidates to mediate the antiproliferative effect of FAP48. FAP48 affects neither the calcineurin-dependent nuclear factor of activated T cells (NFAT)1 nor JNK͞p38-dependent pathways that mediate immunosuppression by FK506. However, contrary to FK506, which blocks IL2 synthesis, we observed that FAP48 -FKBP complexes increase IL2 production, thus revealing a previously uncharacterized aspect of the immunosuppressive mechanism of FK506.T he pharmacological actions of immunosuppressant drugs such as FK506 and rapamycin are mediated in the cell by intracellular proteins named FK506-binding proteins (FKBPs) belonging to the immunophilin family (reviewed in refs. 1-3).The main cytoplasmic FKBP isoform is FKBP12, which, in a complex with FK506, binds to and inhibits the phosphatase calcineurin (4-6). Subsequently, dephosphorylation and nuclear translocation of nuclear factor of activated T cells (NFAT)1 can no longer occur, leading to the inhibition of the transcription of the IL2 gene, IL2 being the major growth factor for T cells (reviewed in ref. 7). In addition, a recent report has demonstrated that immunophilin-FK506 complexes block the JNK and p38 mitogen-activated protein kinases (MAPKs) during T cell activation and also inhibit IL2 synthesis via these pathways (8). The authors showed that direct inhibitors of calcineurin activity had no effect on JNK and p38 activation, suggesting that FK506 leads to immunosuppression via calcineurin-dependent as well as calcineurin-independent pathways.FKBP52 is another member of the FKBP family that was originally found associated with heat shock protein with a molecular mass of 90 kDa (HSP90) in the heterooligomeric forms of steroid receptor complexes (9, 10). FKBP52 displays a modular organization (11-13) and only the NH 2 -terminal part of the protein is responsible for the immunophilin character of the whole protein; it binds FK506 and rapamycin and displays a peptidylprolyl isomerase function characteristic of the immunophilin family (14). Although this NH 2 -terminal part shares high structural and functional homologies with FKBP12, it does not inhibit the phosphatase activity of calc...

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Section: Methodsmentioning

confidence: 99%

The FKBP-associated protein FAP48 is an antiproliferative molecule and a player in T cell activation that increases IL2 synthesis

Krummrei

Baulieu

Chambraud

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…It was first discovered by Faber and colleagues as a component of the untransformed PR complex [48] and has since been found to interact with all SR receptors [17, 49, 50]. Numerous cell-based studies uniformly point to FKBP52 as a positive regulator of SR transcriptional activity [51–53], with the possible exception of ER which appears to be less sensitive to its actions [54].…”

Section: Fkbp52mentioning

confidence: 99%

Chaperoning steroidal physiology: Lessons from mouse genetic models of Hsp90 and its cochaperones

Sánchez

2012

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

100

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The molecular chaperone Hsp90 is abundant, ubiquitous, and catholic to biological processes in eukaryotes, controlling phosphorylation cascades, protein stability and turnover, client localization and trafficking, and ligand-receptor interactions. Not surprisingly, Hsp90 does not accomplish these activities alone. Instead, an ever-growing number of cochaperones have been identified, leading to an explosion of reports on their molecular and cellular effects on Hsp90 chaperoning of client substrates. Notable among these clients are many members of the steroid receptor family, such as glucocorticoid, androgen, estrogen and progesterone receptors. Cochaperones typically associated with the mature, hormone-competent states of these receptors include p23, the FK506-binding protein 52 (FKBP52), FKBP51, protein phosphatase 5 (PP5) and cyclophilin 40 (Cyp40). The ultimate relevance of these cochaperones to steroid receptor action depend on their physiological effects. In recent years, the first mouse genetic models of these cochaperones have been developed. This work will review the complex and intriguing phenotypes so far obtained in genetically-altered mice and compare them to the known molecular and cellular impacts of cochaperones on steroid receptors.

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“…The first TPR protein discovered to associate with steroid receptors was the immunophilin FKBP52 by Faber et al in 1984 [44]. Since then two additional immunophilins and one phosphatase have been determined to associate with the mature steroid receptor complex: FKBP51, Cyp40, and PP5, respectively.…”

Section: Tpr Proteinsmentioning

confidence: 99%

Glucocorticoid receptor physiology

Heitzer

Wolf

Sánchez

et al. 2007

Rev Endocr Metab Disord

202

147

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Glucocorticoid action in cells is mediated by a specific receptor protein, the glucocorticoid receptor (GR). GR is a member of a superfamily of ligand-inducible transcription factors that control a variety of physiological functions; such as, metabolism, development, and reproduction. Unliganded GR is predominantly localized within the cytoplasm but rapidly and efficiently translocates to the nucleus following hormone binding. This review will focus on the intracellular signaling pathway utilized by the GR including the mechanisms that control its intracellular trafficking, hormone binding and transcriptional regulation. Many receptor-interacting proteins are involved in distinct steps in GR signal transduction, each with a unique mechanism to regulate receptor action and providing potential drug targets for the manipulation of cellular responses to glucocorticoids.

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Development of a monoclonal antibody to the rabbit 8.5S uterine progestin receptor

Cited by 54 publications

References 2 publications

The FKBP-associated protein FAP48 is an antiproliferative molecule and a player in T cell activation that increases IL2 synthesis

The FKBP-associated protein FAP48 is an antiproliferative molecule and a player in T cell activation that increases IL2 synthesis

Chaperoning steroidal physiology: Lessons from mouse genetic models of Hsp90 and its cochaperones

Glucocorticoid receptor physiology

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