Journal ArticleDOI
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
Shuhei Matsuoka,Bryan A. Ballif,Agata Smogorzewska,Agata Smogorzewska,E. Robert McDonald,Kristen E. Hurov,Ji Luo,Corey E. Bakalarski,Zhenming Zhao,Nicole L. Solimini,Yaniv Lerenthal,Yosef Shiloh,Steven P. Gygi,Stephen J. Elledge +13 more
TLDR
A large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR is performed and more than 900 regulated phosphorylation sites encompassing over 700 proteins are identified.Abstract:
Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.read more
Citations
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Journal ArticleDOI
CUX1 transcription factor is required for optimal ATM/ATR-mediated responses to DNA damage
Charles Vadnais,Sayeh Davoudi,Mojdeh Afshin,Ryoko Harada,Rachel Dudley,Pier-Luc Clermont,Elliot Drobetsky,Alain Nepveu +7 more
TL;DR: The results indicate that CUX1 regulates a transcriptional program that is necessary to mount an efficient response to mutagenic insult, and ensures not only the proper duplication and segregation of the genetic material, but also the preservation of its integrity.
Journal ArticleDOI
Phosphoproteomics--finally fulfilling the promise?
TL;DR: The development of phosphopeptide/protein analysis by mass spectrometry and the various techniques used to enrich phosphopePTides/proteins are covered and the future of phosphoproteomic research is speculated, now that the goal of generating global phosphoprotein datasets has been realized.
Journal ArticleDOI
α-Internexin expression identifies 1p19q codeleted gliomas
François Ducray,Emmanuelle Crinière,Ahmed Idbaih,Karima Mokhtari,Y. Marie,Sophie Paris,Soledad Navarro,Florence Laigle-Donadey,Caroline Dehais,Joëlle Thillet,Khê Hoang-Xuan,J.-Y. Delattre,M. Sanson +12 more
TL;DR: In this article, α-internexin (INA) expression was evaluated by immunohistochemistry in a series of 122 gliomas, and correlated to the 1p19q codeletion, a favorable prognostic marker of oligodendroglial tumors.
Journal ArticleDOI
JNK1 Phosphorylation of Cdt1 Inhibits Recruitment of HBO1 Histone Acetylase and Blocks Replication Licensing in Response to Stress
Benoit Miotto,Kevin Struhl +1 more
TL;DR: Regulated and reciprocal recruitment of the HBO1 coactivator to target genes and replication origins via JNK-mediated phosphorylation of the recruiting transcription and replication licensing factors coordinates the transcriptional and DNA replication response to cellular stress.
Journal ArticleDOI
Phosphorylation of the leukemic oncoprotein EVI1 on serine 196 modulates DNA binding, transcriptional repression and transforming ability.
Daniel J. White,Richard D. Unwin,Eric Bindels,Andrew Pierce,Hsiang Ying Teng,Joanne Muter,Brigit F. Greystoke,Tim D.D. Somerville,John R. Griffiths,Simon C. Lovell,Tim C. P. Somervaille,Ruud Delwel,Anthony D. Whetton,Stefan Meyer +13 more
TL;DR: Ex vivo EVI1 function is modulated by phosphorylation of the first zinc finger domain, which is associated with significantly higher Evi1-trancript levels compared with WT-EVI1 orEVI1-S196A, mimicking S196 non-phosphorylated EVI 1.
References
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Journal ArticleDOI
The DNA damage response: putting checkpoints in perspective
TL;DR: The inability to repair DNA damage properly in mammals leads to various disorders and enhanced rates of tumour development, and this work has shown that direct activation of DNA repair networks is needed to correct this problem.
Journal ArticleDOI
Cell-cycle checkpoints and cancer
Michael B. Kastan,Jiri Bartek +1 more
TL;DR: All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation, and how cells respond to DNA damage are critical determinants of whether that individual will develop cancer.
Journal ArticleDOI
DNA damage-induced activation of p53 by the checkpoint kinase Chk2.
Atsushi Hirao,Young-Yun Kong,Shuhei Matsuoka,Andrew Wakeham,Jürgen Ruland,Hiroki Yoshida,Dou Liu,Stephen J. Elledge,Tak W. Mak +8 more
TL;DR: Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding, and provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.
Journal ArticleDOI
Immunoaffinity profiling of tyrosine phosphorylation in cancer cells
John Rush,Albrecht Moritz,Kimberly Lee,Ailan Guo,Valerie Goss,Erik Spek,Hui Zhang,Hui Zhang,Hui Zhang,Xiang-ming Zha,Xiang-ming Zha,Xiang-ming Zha,Roberto D. Polakiewicz,Michael J. Comb +13 more
TL;DR: Applying this approach to several cell systems, including cancer cell lines, shows it can be used to identify activated protein kinases and their phosphorylated substrates without prior knowledge of the signaling networks that are activated, a first step in profiling normal and oncogenic signaling networks.
Journal Article
Global Analysis of Protein Phosphorylation in Yeast
Jason Ptacek,Geeta Devgan,Gregory A. Michaud,Heng Zhu,Xiaowei Zhu,Joseph Fasolo,Hong Guo,Ghil Jona,Ashton Breitkreutz,Richelle Sopko,Rhonda R. McCartney,Martin C. Schmidt,Najma Rachidi,Soo-Jung Lee,Angie S. Mah,Lihao Meng,Michael J. R. Stark,David F. Stern,Claudio De Virgilio,Mike Tyers,Brenda J. Andrews,Mark Gerstein,Barry Schweitzer,Paul F. Predki,Michael Snyder +24 more
TL;DR: The in vitro substrates recognized by most yeast protein kinases are described, with the use of proteome chip technology, and these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.