Cloning and Uterus/Oviduct-specific Expression of a Novel Estrogen-regulated Gene (ERG1)

Chen, Dahu; Xu, Xueping; Zhu, Lian; Angervo, Maarit; Li, Quanxi; Bagchi, Milan K.; Bagchi, Indrani C.

doi:10.1074/jbc.274.45.32215

Cited by 24 publications

(14 citation statements)

References 39 publications

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“…Putative functional motifs contained within RatUO-44 are identified as CUB domains and a zona-pellucida (ZP) domain. An identical cDNA sequence of a rat estrogen-regulated gene, ERG1 (GenBank Accession number AF167170) also reported similar findings with the indication of a signal peptide at the amino-terminal (N-terminal) and a transmembrane domain at the carboxyl-terminal (Cterminal) (Chen et al, 1999). A mouse homolog of RatUO-44 (GenBank Accession number U69699) annotated as an integral membrane-associated protein-1 (Itmap1) has also been isolated from a pregnant mouse uterus cDNA library, their study proposed that the protein plays an important role in uterine events during late pregnancy (Kasik, 1998).…”

Section: Introductionsupporting

confidence: 51%

“…A bioinformatics assessment under the secreted protein discovery inititive (SPDI) had previously identified more than 1000 secreted and transmembrane human proteins and HuUO-44D was one of these proteins (Clark et al, 2003). The sequence of HuUO-44D transcript was also annotated as human ERG1 (GenBank Accession number NM022034); however, the publication cited in this annotation contains only data from the rat ERG1 (GenBank Accession number AF167170) (Chen et al, 1999), no mention of the human homolog was made in their report. HuUO-44B, -C and -D contained only an internally spliced exon 4A of 151 bp (Figure 2), while all three 5 0 RACE contigs contained longer exon 4 that varies in sizes (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

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Molecular cloning, characterization and isolation of novel spliced variants of the human ortholog of a rat estrogen-regulated membrane-associated protein, UO-44

Leong

et al. 2004

Oncogene

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We have previously reported the characterization of an estrogen-regulated rat uterine-ovarian-specific complementary DNA (UO-44). To understand the involvement of this protein in the initiation and progression of human ovarian and uterine cancers, we now report the cloning and characterization of the human ortholog (HuUO-44). HuUO-44 is mapped to chromosome 10q26.13 and contains nine exons. Multiple tissue Northern blot detected two HuUO-44 transcripts of approximately 2 and 3 kb in the pancreas. RT-PCR demonstrated that HuUO-44 undergoes a complex series of alternative splicing events between exons 2 and 6 that yielded four novel splice variants, HuUO-44A, HuUO-44B, HuUO-44C and HuUO-44D. Putative functional motifs identified in HuUO-44 are two CUB domains and a zona-pellucida domain. Transfection studies demonstrated the membrane-associated nature of HuUO-44. By immunohistochemistry, HuUO-44 was located to the normal ovarian and ovarian tumor epithelial cells; in NIH-OVCAR3 ovarian cancer cells, HuUO-44 was detected only at the leading edge of the dividing cells. Most importantly, a marked loss in cell attachment and proliferation was observed in NIH-OVCAR3 cells cultured in the presence of a polyclonal HuUO-44 antiserum. These findings suggest the potential role of HuUO-44 in cell motility, cell-cell interactions and/or interactions with the extracellular matrices.

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Section: Introductionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Molecular cloning, characterization and isolation of novel spliced variants of the human ortholog of a rat estrogen-regulated membrane-associated protein, UO-44

Leong

et al. 2004

Oncogene

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“…The localization of the spermligand active high-mannose-type chain in bovine ZPB and ZPC should be clarified. Besides the zona proteins, the ZP domain has been found in several proteins: TGF-b type III receptor (betaglycan) from fetal and adult tissues [28,29], uromodulin (urinary Tamm-Horsfall glycoprotein of pregnant woman) [30], the major zymogen granule membrane protein (GP-2) [31], and the proteins in the uterus and oviduct [32,33]. Furthermore, tectorins in the tectorial membranes responsible for hearing also have a ZP domain [34,35].…”

Section: Discussionmentioning

confidence: 99%

Localization of N‐linked carbohydrate chains in glycoprotein ZPA of the bovine egg zona pellucida

Ikeda

Yonezawa

Naoi

et al. 2002

European Journal of Biochemistry

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The zona pellucida, a transparent envelope surrounding the mammalian oocyte, consists of three glycoproteins, ZPA, ZPB and ZPC, and plays a role in sperm-egg interactions. In bovines, these glycoproteins cannot be separated unless the acidic N-acetyllactosamine regions of the carbohydrate chains are removed by endo-b-Galactosidase digestion. Endo-b-Galactosidase-digested ZPB retains stronger spermbinding activity than ZPC. It is still unclear whether ZPA possesses significant activity. Recently, we reported that bovine sperm binds to Man 5 GlcNAc 2 , the neutral N-linked chain in the cow zona proteins. In this study, we investigated the localization of the sperm-ligand active high-mannosetype chain and the acidic complex-type chains in bovine ZPA. Three N-glycopeptides of ZPA, containing an N-glycosylation site at Asn83, Asn191 and Asn527, respectively, were obtained from endo-b-Galactosidase-digested ZPA. Of these glycosylation sites, only Asn527 is present in the ZP domain common to all the zona proteins. The carbohydrate structures of the N-linked chains obtained from each N-glycopeptide were characterized by two-dimensional sugar mapping analysis, while considering the structures of the N-linked chains of the zona protein mixture reported previously. Acidic complex-type chains were found at all three N-glycosylation sites, while Man 5 GlcNAc 2 was found at Asn83 and Asn191, but there was very little of this spermligand active chain at Asn527 in the ZP domain of ZPA.Keywords: glycoprotein; N-linked carbohydrate chain; sperm ligand; zona pellucida; ZP domain.The mammalian oocyte is coated with a transparent matrix called the zona pellucida. This matrix plays various roles in the early phase of fertilization: species-specific sperm binding, blocking polyspermy, and protecting the embryo until implantation [1,2]. The zona is composed of three glycoproteins, called ZPA, ZPB and ZPC in the order of the size of their cDNAs [3], and their carbohydrate chains are responsible for species-specific sperm-zona binding [1,4].In the pig, the carbohydrate structures of O-linked chains of zona protein mixture [5,6] and the acidic and neutral N-linked chains of ZPB/ZPC mixture [7,8] are well characterized. Sperm-binding activity has been ascribed to the O-linked chains of the zona protein mixture [9] or to the neutral N-linked chains obtained from the ZPB/ZPC mixture [8]. We have shown that the triantennary/tetraantennary chains of the ZPB/ZPC mixture possess greater activity than the diantennary chains [10]. The triantennary/ tetraantennary chains of ZPB are localized at Asn220 in the N-terminal region [10]. Moreover, the isolated N-terminal peptide of ZPB including Asn220 has sperm-binding activity [11]. Yurewicz et al. [12] showed that ZPB and ZPC form heterocomplexes that have sperm-binding activity, but that monomeric ZPB or ZPC does not exhibit this activity. These results suggest that ZPC contributes to the expression of the sperm-binding activity of the neutral N-linked chain of ZPB. In ZPC, the triantennary/tetraante...

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“…In general, UO-44 expression is upregulated in the uterus during cell proliferation induced by estrogens but downregulated during cell stress by pure anti-estrogen (ICI 182780) (Chen et al, 1999;Huynh et al, 2001). More specifically, the human orthologue of UO-44 (HuUO-44) is involved in ovarian cancer cell attachment and proliferation (Leong et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Primary translation product of the UO-44 gene encodes a polypeptide of 607 amino acids, which contains a secretory signal sequence, two CUB domains, a zona pellucida domain and a transmembrane region (Chen et al, 1999). UO-44 has been implicated in diverse physiological functions, including pregnancy development (Kasik, 1998;Chen et al, 1999), protection against severity of pancreatitis (Imamura et al, 2002) and cell adhesion (Huynh et al, 2001). In our previous study, we have isolated alternatively spliced variants of the human UO-44 gene, which may function to regulate its gene expression (Leong et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro

et al. 2006

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Ovarian cancer is currently the second leading cause of gynecological malignancy and cisplatin or cisplatin-based regimens have been the standard of care for the treatment of advance epithelial ovarian cancers. However, the efficacy of cisplatin treatment is often limited by the development of drug resistance either through the inhibition of apoptotic genes or activation of antiapoptotic genes. We have previously reported the overexpression of human UO-44 (HuUO-44) in ovarian cancers and the HuUO-44 antisera markedly inhibited NIH-OVCAR3 ovarian cancer cell attachment and proliferation (Oncogene 23: 5707-5718, 2004). In the present study, we observed through the cancer cell line profiling array that the expression of HuUO-44 was suppressed in the ovarian cancer cell line (SKOV-3) after treatment with several chemotherapeutic drugs. Similarly, this suppression in HuUO-44 expression was also correlated to the cisplatin sensitivity in two other ovarian cancer cell lines NIH-OVCAR3 and OV-90 in a dose-dependent manner. To elucidate the function of HuUO-44 in cisplatin chemoresistance in ovarian cancer cell, small interfering RNAs (siRNAs) were employed to mediate HuUO-44 silencing in ovarian cancer cell line, NIH-OVCAR3. HuUO-44 RNA interference (RNAi) resulted in the inhibition of cell growth and proliferation. Importantly, HuUO-44 RNAi significantly increased sensitivity of NIH-OVCAR3 to cytotoxic stress induced by cisplatin (Po0.01). Strikingly, we have also demonstrated that overexpression of HuUO-44 significantly conferred cisplatin resistance in NIH-OVCAR3 cells (Po0.05). Taken together, UO-44 is involved in conferring cisplatin resistance; the described HuUO-44-specific siRNA oligonucleotides that can potently silence HuUO-44 gene expression may prove to be valuable pretreatment targets for antitumor therapy or other pathological conditions that involves aberrant HuUO-44 expression.

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Cloning and Uterus/Oviduct-specific Expression of a Novel Estrogen-regulated Gene (ERG1)

Cited by 24 publications

References 39 publications

Molecular cloning, characterization and isolation of novel spliced variants of the human ortholog of a rat estrogen-regulated membrane-associated protein, UO-44

Molecular cloning, characterization and isolation of novel spliced variants of the human ortholog of a rat estrogen-regulated membrane-associated protein, UO-44

Localization of N‐linked carbohydrate chains in glycoprotein ZPA of the bovine egg zona pellucida

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro

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