Synthesis and Processing of Ovine Trophoblast Protein-1 and Bovine Trophoblast Protein-1, Conceptus Secretory Proteins Involved in the Maternal Recognition of Pregnancy*

Anthony, Russell V.; Helmer, Stephen D.; Sharif, Setareh F.; Roberts, R. Michael; Hansen, Peter J.; Thatcher, W.W.; Bazer, Fuller W.

doi:10.1210/endo-123-3-1274

Cited by 58 publications

(26 citation statements)

References 27 publications

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“…Multiple genes encode for IFN-T [2,[19][20][21][22][23], and at least three to four distinct gene products are expressed in sheep and cattle [24][25][26][27]. The primary amino acid sequences of these ovIFN-T variants, inferred from the nucleotide sequences of their cDNA or genes, differ by as much as 13% [2,[19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Different Ovine Interferon-Tau Genes Are Not Expressed Identically and Their Protein Products Display Different Activities1

Ealy

Green

Alexenko

et al. 1998

Biology of Reproduction

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Interferon tau (IFN-tau) proteins are secreted by the ovine conceptus for a few days before definitive attachment of the trophoblast to the uterine epithelium and act to prolong luteal life span. Multiple genes encode for IFN-tau in sheep, but it remains unclear which genes are expressed during early pregnancy and whether the proteins encoded by these genes are equipotent. Three distinct ovine (ov) IFN-tau gene variants, p3, p6, and s4, were examined to determine whether they differed in gene expression and whether the proteins displayed different biological activities. By using RNase protection assays, full-length protected fragments were detected for p3 and p6 in approximately similar proportions in conceptuses flushed from the uterus at Days 12-13, Days 15-16, and Days 18-19 of pregnancy, but the amount of full-length protected s4 transcripts was 10% to 20% of that for p3 and p6. Partially protected probe fragments were also evident, presumably from probe hybridization to related ovIFN-tau transcripts. Recombinant proteins were generated and exhibited 34.2 (p3), 8.4 (p6), and 11.9 (s4) units (x 10(-7)) of activity per milligram of protein when tested on Madin-Darby bovine kidney cells. Antiproliferative activity on human Daudi cells varied considerably between the interferons, with p3 being 2000-fold more potent than s4. The interferons were injected into the uterine lumen of ewes from 10 to 18 days postestrus. The functional life span of the corpus luteum (CL) was increased (p = 0.02) by either 300 microg/day p3 (31.7 +/- 7.8 days) or 300 microg/day p6 (25.5 +/- 4.2 days), but not by 300 microg/day s4 (19.2 +/- 2.9 days), when compared to controls (15.8 +/- 0.6 days). Injection of 1 mg/day s4 did, however, increase (p = 0.02) CL life span (23.5 +/- 4.1 days). These data suggest that IFN-tau genes are not equally expressed in trophectoderm and that ovIFN-tau genes encode for proteins with significantly different biological potency.

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Section: Introductionmentioning

confidence: 99%

Different Ovine Interferon-Tau Genes Are Not Expressed Identically and Their Protein Products Display Different Activities1

Ealy

Green

Alexenko

et al. 1998

Biology of Reproduction

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“…Furthermore, bTP-1 is immunologically related to ovine trophoblast protein-1 (oTP-1; Helmer et al, 1987), which is responsible for luteal maintenance in the ewe (Godkin et al, 1984). The bTP-1 complex consists of 7 isoelectric variants (pi = 5-5 to 5-7) of N-linked glycoproteins in two molecular weight classes; one of Mr 22 000 and high mannose content and the other of M, 24 000 and complex carbohydrate content (Helmer et al, 1987Anthony et al, 1988). The present study was designed to evaluate the role of bTP-1 in extension of CL lifespan by purifying bTP-1 and testing its efficacy as an antiluteolysin when infused into the uterine lumen during Days 15-5-21 of the oestrous cycle.…”

Section: Introductionmentioning

confidence: 99%

Intrauterine infusion of highly enriched bovine trophoblast protein-1 complex exerts an antiluteolytic effect to extend corpus luteum lifespan in cyclic cattle

Helmer

Hansen²,

Thatcher³

et al. 1989

Reproduction

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“…It remains unclear whether this outcome is the result of posttranslational processing or of differentially spliced forms of DLX3. The broad band of IFNT with an approximate molecular weight of 21 000 Da probably results from a combination of variable glycosylation of this glycoprotein and the presence of multiple isoforms[36].…”

mentioning

confidence: 99%

The Role of Homeobox Protein Distal-Less 3 and Its Interaction with ETS2 in Regulating Bovine Interferon-Tau Gene Expression-Synergistic Transcriptional Activation with ETS21

Ezashi

Das

Gupta

et al. 2008

Biology of Reproduction

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Distal-less 3 (DLX3), a homeodomain transcription factor required for placental development in the mouse, modestly transactivates hCG-alpha subunit gene (hCGA) expression in human choriocarcinoma cells. Because hCG and interferon-tau (IFNT) are expressed in trophectoderm of primates and ruminants, respectively, we have tested the hypothesis that DLX3 regulates the genes for IFNT (IFNT). A bovine IFNT1 promoter (-457 to +66), linked to a luciferase (luc) reporter, was transactivated approximately 20-fold by overexpressing DLX3 in human JAr cells. Elimination of a potential DLX3-binding site (-54 GATAATGAG -46) by either truncation or mutagenesis abolished this effect. A sequence (-59 to -44) encompassing this site bound DLX3 specifically. Coexpression of DLX3 and ETS2, which is known to be a key regulator of IFNT expression, increased reporter activity by more than 250-fold, whereas deletion of the established ETS2 site (-79 to -70) eliminated the ability of DLX3 to transactivate the gene. Conversely, mutation of the DLX3 site significantly reduced the transactivational effects of ETS2. Both DLX3 and ETS2 are coexpressed in JAr cells and in an IFNT-producing, bovine trophoblast cell line, CT-1. The two can be immunoprecipitated together as a complex from CT-1 cells, and RNAi-mediated, partial knockdown of DLX3 expression reduced the production of IFNT by approximately 50+. Together, these results suggest that DLX3 has a central role in controlling IFNT gene expression by associating with ETS2 on the IFNT promoter.

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Synthesis and Processing of Ovine Trophoblast Protein-1 and Bovine Trophoblast Protein-1, Conceptus Secretory Proteins Involved in the Maternal Recognition of Pregnancy*

Cited by 58 publications

References 27 publications

Different Ovine Interferon-Tau Genes Are Not Expressed Identically and Their Protein Products Display Different Activities1

Different Ovine Interferon-Tau Genes Are Not Expressed Identically and Their Protein Products Display Different Activities1

Intrauterine infusion of highly enriched bovine trophoblast protein-1 complex exerts an antiluteolytic effect to extend corpus luteum lifespan in cyclic cattle

The Role of Homeobox Protein Distal-Less 3 and Its Interaction with ETS2 in Regulating Bovine Interferon-Tau Gene Expression-Synergistic Transcriptional Activation with ETS21

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