MAPKinase signaling and AP-1-regulated gene expression in cellular responses to DNA damage
Hamdi, M.
Citation
Hamdi, M. (2008, October 29). MAPKinase signaling and AP-1-regulated gene expression in cellular responses to DNA damage. Retrieved from https://hdl.handle.net/1887/13208
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
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MAPKinase signaling and AP-1-regulated gene expression in
cellular responses to DNA damage
MAPKinase signaling and AP-1-regulated gene expression in cellular responses to DNA damage
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof.mr. P.F. van der Heijden,
volgens besluit van het College voor Promoties
te verdedigen op woensdag 29 oktober 2008
klokke 16:15 uur
door
Mohamed Hamdi
geboren te Beni Said (Marokko)
in 1974
Promotiecommissie
Promotor: Prof. Dr. P. ten Dijke
Co-promotor: Dr. ir. J.A.F. van Dam
Referent: Prof. Dr. B. van de Water
Overige leden: Prof. Dr. A.A. van Zeeland
Prof. Dr. R.H. Medema (Universiteit Utrecht)
The research presented in this thesis was performed at the department of Molecular Cell Biology, Leiden Medical Centre, Leiden, The Netherlands. This work was supported by grants from the Netherlands Organisation for Scientific Research (NWO), the Dutch Cancer Society (KWF) and the Radiation Protection, Biomed and TMR Programs of the European Community.
Contents
Chapter I General Introduction 9
Introduction to this thesis 24
Chapter II Induction of ATF3 by ionizing radiation is mediated via 33 a signaling pathway that includes ATM, Nibrin1, stress-
induced MAPkinases and ATF-2
Chapter III DNA damage in transcribed genes induces apoptosis 43 via the JNK pathway and the JNK-phosphatase MKP-1
Chapter IV ATF3 and Fra1 have opposite functions in JNK- and ERK- 55 dependent DNA damage responses
Chapter V Inhibition of fra1 by the JNK-Jun pathway can protect cells 67 against genotoxic stress
Chapter VI Summary and discussion 85
Samenvatting 89
Curriculum Vitae 92
