Isolation and Characterization of a Folate Receptor-directed Metalloprotease from Human Placenta

Yang, Xiao Yan; Mackins, Janet Y.; Li, Qing Jun; Antony, Asok

doi:10.1074/jbc.271.19.11493

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…Soluble extracellular forms of FR-α and FR-β are produced by different mechanisms including the action of membrane or intracellular proteases and phospholipase [18][19][20][21][22].…”

Section: Structure and Function Of Frsmentioning

confidence: 99%

The folate receptor: What does it promise in tissue-targeted therapeutics?

Salazar

Ratnam

2007

Cancer Metastasis Rev

313

269

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For over a decade the folate receptor has been intensively investigated as a means for tumor-specific delivery of a broad range of experimental therapies including several conceptually new treatments. Despite a few set backs in clinical trials, the literature is replete with encouraging in vitro and pre-clinical studies of gynecological and other tumors and more therapeutic approaches are ready for clinical testing. Recent studies have added myelogenous leukemias to the list of candidate cancers for FR-targeted therapies. Each approach faces unique challenges in translation that could be addressed through a mechanistic understanding of the function and expression of the receptor in the appropriate experimental systems and by improvements in the technology. This review discusses FR in the context of positive recent developments in broad areas of FR-targeted therapy and attempts to highlight its potential and the anticipated challenges.

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“…Soluble extracellular forms of FR-α and FR-β are produced by different mechanisms including the action of membrane or intracellular proteases and phospholipase [18][19][20][21][22].…”

Section: Structure and Function Of Frsmentioning

confidence: 99%

The folate receptor: What does it promise in tissue-targeted therapeutics?

Salazar

Ratnam

2007

Cancer Metastasis Rev

313

269

View full text Add to dashboard Cite

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“…1 and 2). Human placenta is rich in FR and was the source from which FR were first isolated to apparent homogeneity as a truncated species (3) through the action of an endogenous metalloprotease (4,5). The full-length FR species that are anchored to the membrane by glycosyl phosphatidylinositol anchoring (6) play a crucial role in transplacental maternal-to-fetal transport of folate (7).…”

Section: Folate Receptors (Fr)mentioning

confidence: 99%

Isolation and Characterization of a Folate Receptor mRNA-binding trans-Factor from Human Placenta

Xiao¹,

Tang²,

Mackins³

et al. 2001

Journal of Biological Chemistry

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The interaction of an 18-base cis-element in the 5-untranslated region of human folate receptor (FR)-␣ mRNA with a cytosolic trans-factor protein is critical for the translation of FR (Sun, X.-L., and Antony, A. C. (1996) J. Biol. Chem. 271, 25539 -25547). This trans-factor was isolated to apparent homogeneity as a 43-and 38-kDa doublet from human placenta using poly(U)-Sepharose, followed by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electro-elution as major purification steps. Amino acid microsequencing of two cyanogen bromide-generated peptide fragments of the 43-kDa trans-factor revealed complete identity with 43-kDa heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1). Purified specific rabbit anti-hnRNP E1 peptide antibodies (generated against a synthetic oligopeptide that was not represented in microsequenced peptides of the trans-factor) also recognized the purified trans-factor on Western blots. Conversely, the 18-base FR RNA cis-element also bound hnRNP E1 protein on Northwestern blots. Moreover, a 19-base RNA ciselement in the 3-untranslated region of 15-lipoxygenase mRNA that is known to bind hnRNP E1 also interacted with placental 43-kDa trans-factor. In addition, several murine tissues containing a hnRNP E1-related protein (also known as ␣CP-1) readily interacted with the 18-base FR RNA cis-element. Finally, anti-hnRNP E1 antibodies specifically inhibited translation of FR in vitro in a dose-dependent manner, and the antibody effect could be reversed in a dose-dependent manner by either purified trans-factor or hnRNP E1. Collectively, the data favor identity of the FR mRNA-binding trans-factor and hnRNP E1, confirm its critical role in the translation of FR, and highlight yet another role of multifunctional hnRNP E1 in eukaryotic mRNA regulation.

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“…The FR-a-targeted immunologic therapies include bifunctional antibodies and antibody-interleukin chimeras, peptide and DNA vaccines, and more innovative agents such as dual-specific T cells and folate-hapten conjugates. A portion of the FR-a expressed on the cell surface is released in a soluble form by the combined action of a membrane-associated protease and glycosyl-phosphatidylinositol-specific phospholipase (19)(20)(21)(22). Soluble FR-a is low or undetected in normal human sera, and therefore, the protein shed into the circulation is a potential serum marker for FR-a-positive tumors (23).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Folate Receptor α Expression in Tumor Cells Through the Glucocorticoid Receptor: A Promising Means to Improved Tumor Detection and Targeting

et al. 2005

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The utility of the folate receptor (FR) type A, in a broad range of targeted therapies and as a diagnostic serum marker in cancer, is confounded by its variable tumor expression levels. FR-A, its mRNA and its promoter activity were coordinately up-regulated by the glucocorticoid receptor (GR) agonist, dexamethasone. Optimal promoter activation which occurred at <50 nmol/L dexamethasone was inhibited by the GR antagonist, RU486, and was enhanced by coactivators, supporting GR mediation of the dexamethasone effect. The dexamethasone response of the FR-A promoter progressed even after dexamethasone was withdrawn, but this delayed effect required prior de novo protein synthesis indicating an indirect regulation. The dexamethasone effect was mediated by the G/C-rich (Sp1 binding) element in the core P4 promoter and was optimal in the proper initiator context without associated changes in the complement of major Sp family proteins. Histone deacetylase (HDAC) inhibitors potentiated dexamethasone induction of FR-A independent of changes in GR levels. Dexamethasone/HDAC inhibitor treatment did not cause de novo FR-A expression in a variety of receptornegative cells. In a murine HeLa cell tumor xenograft model, dexamethasone treatment increased both tumor-associated and serum FR-A. The results support the concept of increasing FR-A expression selectively in the receptor-positive tumors by brief treatment with a nontoxic dose of a GR agonist, alone or in combination with a well-tolerated HDAC inhibitor, to increase the efficacy of various FR-A-dependent therapeutic and diagnostic applications. They also offer a new paradigm for cancer diagnosis and combination therapy that includes altering a marker or a target protein expression using general transcription modulators. (Cancer Res 2005; 65(10): 4431-41)

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Isolation and Characterization of a Folate Receptor-directed Metalloprotease from Human Placenta

Cited by 18 publications

References 31 publications

The folate receptor: What does it promise in tissue-targeted therapeutics?

The folate receptor: What does it promise in tissue-targeted therapeutics?

Isolation and Characterization of a Folate Receptor mRNA-binding trans-Factor from Human Placenta

Enhancement of Folate Receptor α Expression in Tumor Cells Through the Glucocorticoid Receptor: A Promising Means to Improved Tumor Detection and Targeting

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