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Untersuchte Arbeit:
Seite: 25, Zeilen: 2-19
Quelle: Lok and Loh 1998
Seite(n): 166, 167, 168, Zeilen: 166: l. Spalte: 2ff; 167: r. Spalte: 8ff; 168: Abbildung
Kuhn and coworkers reported the first genomic clone for the transferrin receptor by expression and cloning techniques (Kuhn, L.C. et al, 1984). The human TfR gene was found to contain at least 19 exons distributed over 31 kb of DNA and contains a translated region of 2,280 nucleotides in their respective cDNA clones.

TfR gene transcription is activated during cell proliferation (Seiser, C. et al, 1993), cell transformation (Beard, P. et al, 1991) and differentiation of immature erythroid cells to hemoglobin synthesizing cells (Chan, R.Y.Y. et al, 1994, Chan, L.N. et al, 1992). On the other hand, gene transcription is comparatively inactive in the quiescent state of the cells, that is during growth arrest and terminal differentiation in the nonerythroid cells (Lok, C.N. et al, 1996). TfR gene transcription is believed to be controlled by cellular signals involved in the cell growth and differentiation, resulting in the expression of TfR for iron demand during cell proliferation or heme synthesis. The TfR gene promoter region (fig. 1.10) is GC-rich and contains a TATA box about 30 bp upstream from the known transcriptional start site. A consensus SP-1/GC-rich sequence is located near the TATA box and a sequence as short as 47 bp upstream of the transcriptional start site has been found to be sufficient for driving the basal transcription of the reporter gene as shown by reporter gene assays (Owen, D. et al, 1987).

Scr 025a diss.png

Fig. 2.5. TfR gene promoter region. Part of the TfR promoter region that is critical for its expression. The underlined sequences represent elements similar to certain consensus cisacting elements. Sequence similarity to consensus regulatory cis-elements and putative binding factors are indicated (see text for explanation). Bold typeface identifies bases identical to the TfR gene elements (Sieweke, M.H. et al, 1996, Ouyang, Q. et al, 1993, Roberts, M.R. et al, 1994). CRE = cAMP-responsive element; CREB = CREbinding protein; PSE = proximal sequence element.

By expression cloning techniques, Schneider and coworkers first isolated cDNA clones of TfR in MOLT-4 cells, and later Kuhn and coworkers [8] reported the first genomic clone for the receptor. The human TfR gene was found to contain at least 19 exons distributed over 31 kb of DNA. Both groups reported a translated region of 2,280 nucleotides in their respective cDNA clones.

[Seite 167]

In general, the gene transcription is activated during cell proliferation [120, 130, 131, 146], cell transformation [147] and differentiation of immature erythroid cells to hemoglobinsynthesizing cells [41, 45]. On the other hand, gene transcription is comparatively inactive in the quiescent state of the cells, that is during growth arrest and terminal differentiation in the nonerythroid cells [148–150]. TfR gene transcription is believed to be controlled by cellular signals involved in the cell growth and differentiation, resulting in the expression of TfR for iron demand during cell proliferation or heme synthesis.

[...] The TfR gene promoter region (fig. 3) is GC-rich and contains a TATA box about 30 bp upstream from the known transcriptional start site. A consensus SP-1/GC-rich seqence is located near the TATA box. [...] By reporter gene assays, a sequence as short as 47 bp upstream of the transcriptional start site has been found to be sufficient for driving the basal transcription of the reporter gene [121].

[Seite 168]

Scr 025a source.png

Fig. 3. TfR gene promoter region. Part of the TfR promoter region that is critical for its expression. The underlined sequences represent elements similar to certain consensus cisacting elements. Sequence similarity to consensus regulatory cis-elements and putative binding factors are indicated (see text for explanation). Bold typeface identifies bases identical to the TfR gene elements [46, 151, 154]. CRE = cAMP-responsive element; CREB = CREbinding protein; PSE = proximal sequence element.


8 Kuhn LC, McClelland A, Ruddle FH: Gene transfer, expression and molecular cloning of the human transferrin receptor gene. Cell 1984; 37:95–103.

41 Chan RYY, Seiser C, Schulman HM, Kuhn LC, Ponka P: Regulation of transferrin receptor mRNA expression: Distinct regulatory features in erythroid cells. Eur J Biochem 1994;220:683–692.

45 Chan LN, Gerhardt EM: Transferrin receptor gene is hyperexpressed and transcriptionally regulated in differentiating erythroid cells. J Biol Chem 1992;267:8254–8259.

121 Owen D, Kuhn LC: Noncoding 3) sequences of the transferrin receptor gene are required for mRNA regulation by iron. EMBO J 1987; 6:1287–1293.

130 Seiser C, Teixeira S, Kuhn LC: Interleukin-2-dependent transcriptional and post-transcriptional regulation of transferrin receptor mRNA. J Biol Chem 1993;268: 13074–13080.

131 Casey JL, Di Jeso B, Rao K, Klausner RD, Harford JB: Two genetic loci participate in the regulation by iron of the gene for the human transferrin receptor. Proc Natl Acad Sci USA 1988;85:1787– 1791.

146 Kronke M, Leonard W, Depper JM, Greene WC: Sequential expression of genes involved in human T lymphocyte growth and differentiation. J Exp Med 1985;161: 1593–1598.

147 Beard P, Offord E, Paduwat N, Bruggmann H: SV40 activates transcription from the transferrin receptor promoter by inducing a factor which binds to the CRE/AP- 1 recognition sequence. Nucleic Acids Res 1991;25:7117–7123.

148 Alcantara O, Denham CA, Phillips JL, Boldt DH: Transcriptional regulation of transferrin receptor expression by cultured lymphoblastoid T cells treated with phorbol esters. J Immunol 1989;142:1719– 1725.

149 Trepel JB, Colamonici OR, Kelly K, Schwab G, Watt RA, Sauville EA, Jaffe ES, Neckers LM: Transcriptional inactivation of c-myc and the transferrin receptor in dibutyryl cyclic AMP-treated HL-60 cells. Mol Cell Biol 1987;7:2644– 2648.

150 Lok CN, Chan KF, Loh TT: Transcriptional regulation of transferrin receptor gene expression during phorbol ester-induced HL-60 cell differentiation: Evidence for a negative regulatory role of the phorbol ester-responsive elementlike sequence. Eur J Biochem 1996;236:614–619.

151 Ouyang Q, Bommakanti M, Miskimins WK: A mitogen-responsive promoter region that is synergistically activated through multiple signalling pathways. Mol Cell Biol 1993;13:1796–1804.

154 Roberts MR, Han Y, Fienberg A, Hunihan L, Ruddle FH: A DNAbinding activity, TRAC, specific for the TRA element of the transferrin receptor gene copurifies with the KU autoantigen. Proc Natl Acad Sci USA 1994;91:6354–6358.

Anmerkungen

Ein Verweis auf die Quelle fehlt.

Auch die meisten Literaturverweis sind übernommen.

"fig. 1.10" existiert in der untersuchten Arbeit nicht. Gemeint ist wohl Abbildung 2.5., denn diese entspricht der Abbildung 3 der Quelle.

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