A urokinase receptor promoter element (-152/-135) bound with an AP-2-alpha-related protein and SP1 is required for the induction of gene expression by PMA and SRC

The urokinase-type plasminogen activator receptor (u-PAR) promotes extracellular matrix degradation, invasion and metastasis. A first objective of this dissertation was to identify cis-elements and trans-acting factors activating u-PAR gene expression through a previously footprinted (–148/–124) promoter region. Mobility shifting experiments on nuclear extracts of a high u-PAR-expressing colon cancer cell line (RKO) indicated Sp1, Sp3 and a factor similar to, but distinct from, AP-2α bound to an oligonucleotide spanning –152/–135. Mutations preventing the binding of the AP-2α-related factor reduced u-PAR promoter activity. In RKO, the expression of a dominant negative AP-2 (AP-2αB) diminished u-PAR promoter activity, protein and u-PAR mediated laminin degradation. Conversely, u-PAR promoter activity in low u-PAR-expressing GEO cells was increased by AP-2αA expression. PMA treatment, which induces u-PAR expression, caused an increased amount of the AP-2α-related factor-containing complex in GEO, and mutations preventing AP-2α-like and Sp1/Sp3 binding reduced the u-PAR promoter stimulation by PMA. In resected colon cancers, u-PAR protein amounts were related to the amount of the AP-2α-related factor-containing complex. In conclusion, constitutive and PMA- inducible u-PAR gene expression and -proteolysis are mediated partly through transactivation via a promoter sequence (–152/435) bound with an AP-2α-related factor and Sp1/Sp3. ^ A second interest of this dissertation was to determine if a constitutively active Src regulates the transcription of the u-PAR gene, since c-src expression increases invasion in colon cancer. Increased u-PAR protein and laminin degradation paralleling elevated Src activity was evident in SW480 colon cancer cells stably expressing a constitutively active Src (Y- c-src527F). Nuclear run-on experiments indicated that this was due largely to transcriptional activation. While transient transfection of SW480 cells with Y-c-src527F induced a u-PAR-CAT-reporter, mutations preventing Sp1-binding to promoter region –152/435 abolished this induction. Mobility shift assays revealed increased Sp1 binding to region –152/135 with nuclear extracts of Src-transfected SW480 cells. Finally, the amounts of endogenous u-PAR in resected colon cancers significantly correlated with Src-activity. These data suggest that u-PAR gene expression and proteolysis are regulated by Src, this requiring the promoter region (–152/–135) bound with Sp1, thus, demonstrating for the first time that transcription factor Sp1 is a downstream effector of Src. ^

Ms. hebr. oct. 152 - Rashi ʻal ha-Torah

Vorbesitzer: Abraham Merzbacher

Ms. Barth. 152 - Medizinische Sammelhandschrift

Vorbesitzer: Bartholomaeusstift Frankfurt am Main

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 152 - Darstellung des hohen Stellenwerts von Frédéric Chopin in der Musik

u.a.: Ausstellung eines Schopenhauer-Gemäldes in einer Berliner Kunstausstellung;

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 915 - Bemerkungen zu den biographischen Studien zu Schopenhauer

2 Seiten

Ms. Praed. 152 - Contiones

Vorbesitzer: Dominikanerkloster Frankfurt am Main

Ms.Ff.F.Stoltze 3. 152 - Brief von Otto Kanngießer an Friedrich Stoltze

Geburtstags-Glückwünsche, Persönliche Nachrichten

Na 1 Nachlass Max Horkheimer, 518 - Korrespondenzen mit Walter Benjamin (Kopien) (p. VI 5, 152 - 366)

75 Briefe (Kopien) zwischen Max Horkheimer und Walter Benjamin;

Na 1 Nachlass Max Horkheimer, 687 - "Experimental Movie Project", "The Police and Minority Groups" u.a. (p. IX 150.1-17 - IX 152.1-2)

"Experimental Movie Project" (1945-46):; 1. "Below the Surface", Drehbuch des Testfilms, a) als Typoskript vervielfältigt, 46 Blatt, b) als Typoskript vervielfältigt, 26 Blatt, c) als Typoskript vervielfältigt, 26 Blatt, d) als Typoskript vervielfältigt, 26 Blatt "Experimental Movie Project" (1945-46): Memoranden zum Test; 2. 'Notes' 25.4.1946, Typoskript, 1 Blatt; 3. "Memorandum on Experimental Movie Project", 19.4.1946. Typoskript, 3 Blatt; 4. "Memorandum re: 'Below the Surface" (Juli 1945). Typoskript, 2 Blatt; 5. Dore Schary und Allen Rivkin: 'Memorandum, Subject: New Suggested Treatment for 'Below the Surface'", 13.7.1945. Typoskript, 2 Blatt; 6. Hans Richter: "Report about the film script 'Below the surface'", 7. u. 8.7.1945, a) Typoskript, 1 Blatt, b) Typoskript, 1 Blatt; 7. Hans Richter: Bestätigung der Vereinbarung mit dem American Jewish Committee, 3.7.1945. Typoskript, 1 Blatt; 8. "Notes and Suggestions re Experimental Motion Picture", Juni 1945. Typoskript, 2 Blatt; 9. Siegfried Kracauer; "Suggestions for the Dialogue" (4.4.1945). Typoskript, 3 Blatt; 10. "Motion Picture", März 1945. Typoskript, 5 Blatt; 11. "Project on a Test film", a) Typoskript, 4 Blatt, b) Typoskript, 5 Blatt; 12. "Memorandum re: 'Below the Surface'", a) Typoskript, 3 Blatt, b) Typoskript mit eigenhändigen Korrekturen von Theodor W. Adorno, 3 Blatt; "Experimental Movie Project" (1945-46): Korrespondenz zum Test-Film-Projekt:; 13. Friedrich Pollock: 1 Brief an Max Horkheimer, Santa Monica, California, 12.10.1945; 14. Theodor W. Adorno: 2 Briefe an Max Horkheimer, Los Angeles und Santa Monica, California, 1945; 15. Joseph M. Proskauer: 1 Brief von Max Horkheimer, o.O., 29.6.1945, 1 Brief mit Unterschrift an Max Horkheimer, o.O., o.D., 3 Blatt; 16. Alexander Hackenschmied, 1 Brief mit Unterschrift an Max Horkheimer, New York, 19.6.1945, 1 Blatt; 17. Gilbert Gabriel: 1 Brief von John Slawson, o.O., 22.3.1945, 2 Blatt; "The Police and Minority Groups" (1946):; 1. "The Police and Minority Groups". Typoskript, 2 Blatt; 2. Robert W. Kenny: "Police and Minority Groups - an Experiment". Als Typoskript vervielfältigt, 17 Blatt; 3. Davis McEntire, Robert B. Powers: "Police Training Bulletin. A Guide to Race Relations for Police Officers", State of California, 1946, 38 Seiten; Max Horkheimer: "Memorandum on a Study of Race Hatred in Post-War Germany" (1946):; 1. Memorandum, a) Typoskript, 8 Blatt, b) Typoskript mit eigenhändigen und handschriftlichen Korrekturen, 6 Blatt, c) Typoskript, 5 Blatt, d) Teilstück, Typoskript mit eigenhändigen Korrekturen, 1 Blatt e) Typoskript mit eigenhändigen Korrekturen, 5 Blatt, f) Teilstück, Typoskript mit handschriftlichen Korrekturen, 2 Blatt, g) Typoskript mit eigenhändigen Korrekturen, 7 Blatt, h) Teilstück, Typoskript mit eigenhändigen Korrekturen und Ergänzungen, 1 Blatt, i) Typoskript, 2 Blatt; 2. Theodor W. Adorno: "Ad Memorandum Neumann", Manuskript, 3 Blatt;

Ms. lat. oct. 152 - Quaestiones de sacramentis (Qu. 84 - 90)

Vorbesitzer: Johannes Bartholomaei;