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      Renal LRP2 expression in man and chicken is estrogen-responsive

      research-article
      a , a , b , a ,   a , *
      Gene
      Elsevier/North-Holland
      Apo, Apolipoprotein, BRCA1, Breast cancer 1, CK-II, Casein kinase-II, DAPI, 4′,6′-diamidino-2′-phenylindole, ERE, Estrogen responsive element, ER, Estrogen receptor, GAPDH, Glycerinaldehyd-3-phosphat-Dehydrogenase, GFP, Green fluorescent protein, gg, Gallus gallus, Gp330, Glycoprotein 330, GSK3, Glycogen synthase kinase-3, GST, Glutathione S-tranferase, HDL, High-density lipoprotein, HEK-293, Human embryonic kidney cells, HRP, Horseradish peroxidase, hs, Homo sapiens, Ig, Immunoglobulin(s), LA-repeat, LDL receptor type A-repeat, LDL, Low-density lipoprotein, LDL-R, Low-density lipoprotein receptor, LRP, Low-densitiy lipoprotein receptor-related protein, Ni-NTA, nickel-nitrilotriacetic acid, ORF, Open reading frame, PKA, Protein kinase A, PKC, Protein kinase C, RAP, Receptor-associated protein, SDS, Sodium dodecyl sulfate, SHBG, Sex hormone binding globulin, Sp, Stimulating protein, SRE, Sterol-responsive element, VLDL, Very low-density lipoprotein, VLDLR, Very low-density lipoprotein receptor, LRP2, LDL-R gene family, Sex specificity, Estrogen‐responsiveness, Chicken

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          Abstract

          In mammals, low-density lipoprotein receptor-related protein-2 (LRP2) is an endocytic receptor that binds multiple ligands and is essential for a wide range of physiological processes. To gain new insights into the biology of this complex protein, we have initiated the molecular characterization of the LRP2 homolog from an oviparous species, the chicken ( Gallus gallus). The galline LRP2 cDNA encodes a membrane protein of 4658 residues. Overall, the galline and human proteins are 73% identical, indicating that the avian gene has been well conserved over 300 million years. Unexpectedly, LRP2 transcript and protein levels in the kidney of females and estrogen-treated roosters were significantly higher than those in untreated males. The estrogen-responsiveness of avian LRP2 may be related to the dramatic differences in lipoprotein metabolism between mature roosters and laying hens. Newly identified potential estrogen-responsive elements (ERE) in the human and galline LRP2 gene, and additional Sp1 sites present in the promoter of the chicken gene, are compatible with both direct estrogen induction via the classical ligand-induced ERE pathway and the indirect transcription factor crosstalk pathway engaging the Sp1 sites. In agreement with this assumption, estrogen induction of LRP2 was observed not only in primary cultured chicken kidney cells, but also human kidney cell lines. These findings point to novel regulatory features of the LRP2 gene resulting in sex-specific receptor expression.

          Highlights

          ► First molecular characterization of a non-mammalian LRP2 ► LRP2 is highly conserved from chicken to man. ► Induction by estrogen of LRP2 in‐vivo and in cultured kidney cells of chicken and man ► Identification of estrogen-responsive elements in the galline and human genes

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          Most cited references62

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          Characteristics of a human cell line transformed by DNA from human adenovirus type 5.

          Human embryonic kidney cells have been transformed by exposing cells to sheared fragments of adenovirus type 5 DNA. The transformed cells (designated 293 cells) exhibited many of the characteristics of transformation including the elaboration of a virus-specific tumour antigen. Analysis of the polypeptides synthesized in the 293 cells by labelling with 35S-methionine and SDS PAGE showed a variable pattern of synthesis, different in a number of respects from that seen in otheruman cells. On labelling the surface of cells by lactoperoxidase catalysed radio-iodination, the absence of a labelled polypeptide analogous to the 250 K (LETS) glycoprotein was noted. Hybridization of labelled cellular RNA with restriction fragments of adenovirus type 5 DNA indicated transcription of a portion of the adenovirus genome at the conventional left hand end.
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            The role of Sp1 and Sp3 in normal and cancer cell biology.

            Sp1 and Sp3 are transcription factors expressed in all mammalian cells. These factors are involved in regulating the transcriptional activity of genes implicated in most cellular processes. Dysregulation of Sp1 and Sp3 is observed in many cancers and diseases. Due to the amino acid sequence similarity of the DNA binding domains, Sp1 and Sp3 recognize and associate with the same DNA element with similar affinity. However, others and our laboratory demonstrated that these two factors possess different properties and exert different functional roles. Both Sp1 and Sp3 can interact with and recruit a large number of proteins including the transcription initiation complex, histone modifying enzymes and chromatin remodeling complexes, which strongly suggest that Sp1 and Sp3 are important transcription factors in the remodeling chromatin and the regulation of gene expression. In this review, the role of Sp1 and Sp3 in normal and cancer cell biology and the multiple mechanisms deciding the functional roles of Sp1 and Sp3 will be presented. Copyright © 2010 Elsevier GmbH. All rights reserved.
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              LRP: a multifunctional scavenger and signaling receptor.

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                Author and article information

                Journal
                Gene
                Gene
                Gene
                Elsevier/North-Holland
                0378-1119
                1879-0038
                15 October 2012
                15 October 2012
                : 508
                : 1
                : 49-59
                Affiliations
                [a ]Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria
                [b ]Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Währinger Gürtel 18–20, A1090 Vienna, Austria
                Author notes
                [* ]Corresponding author at: Department of Medical Biochemistry, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria. Tel.: + 43 1 4277 61820; fax: + 43 1 4277 9618. marcela.hermann@ 123456meduniwien.ac.at
                Article
                GENE37728
                10.1016/j.gene.2012.07.041
                3443750
                22868208
                f63e4a9a-037e-46f6-b62e-afd4f9fdd98f
                © 2012 Elsevier B.V.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 15 July 2012
                Categories
                Article

                Genetics
                er, estrogen receptor,gsk3, glycogen synthase kinase-3,la-repeat, ldl receptor type a-repeat,sex specificity,vldlr, very low-density lipoprotein receptor,pka, protein kinase a,ere, estrogen responsive element,gapdh, glycerinaldehyd-3-phosphat-dehydrogenase,hs, homo sapiens,sds, sodium dodecyl sulfate,gp330, glycoprotein 330,ldl-r gene family,orf, open reading frame,ig, immunoglobulin(s),apo, apolipoprotein,lrp, low-densitiy lipoprotein receptor-related protein,gst, glutathione s-tranferase,chicken,brca1, breast cancer 1,gfp, green fluorescent protein,ldl, low-density lipoprotein,shbg, sex hormone binding globulin,pkc, protein kinase c,estrogen‐responsiveness,ldl-r, low-density lipoprotein receptor,lrp2,ck-ii, casein kinase-ii,hdl, high-density lipoprotein,ni-nta, nickel-nitrilotriacetic acid,hek-293, human embryonic kidney cells,vldl, very low-density lipoprotein,sre, sterol-responsive element,rap, receptor-associated protein,gg, gallus gallus,dapi, 4′,6′-diamidino-2′-phenylindole,hrp, horseradish peroxidase,sp, stimulating protein

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