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
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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
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N-Myc promotes therapeutic resistance development of neuroendocrine prostate cancer by differentially regulating miR-421/ATM pathway
Yu Yin,Yu Yin,Lingfan Xu,Lingfan Xu,Yan Chang,Yan Chang,Tao Zeng,Xufeng Chen,Aifeng Wang,Jeff Groth,Wen-Chi Foo,Chaozhao Liang,Hailiang Hu,Hailiang Hu,Jiaoti Huang,Jiaoti Huang +15 more
TL;DR: Surprisingly, N-Myc overexpression upregulated ATM expression in C4–2 cells and this upregulation promoted migration and invasion of prostate cancer cells and N- myc differentially regulating miR-421/ATM pathway contributes to ADT resistance and Enzalutamide resistance development respectively.
Journal ArticleDOI
DNA-damage-induced nuclear export of precursor microRNAs is regulated by the ATM-AKT pathway
Guohui Wan,Xinna Zhang,Robert R. Langley,Yunhua Liu,Xiaoxiao Hu,Cecil Han,Guang Peng,Lee M. Ellis,Stephen N. Jones,Xiongbin Lu +9 more
TL;DR: It is shown that nuclear export of pre-miRNAs is accelerated after DNA damage in an ATM-dependent manner, defining an important role of DNA-damage signaling in miRNA transport and maturation.
Journal ArticleDOI
The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxidative stress.
Tae-Sun Kim,Makoto Kawaguchi,Mitsuko Suzuki,Cha-Gyun Jung,Kiyofumi Asai,Yuta Shibamoto,Martin F. Lavin,Kum Kum Khanna,Yutaka Miura +8 more
TL;DR: A novel signaling pathway that links ATM via cAMP-responsive-element-binding protein (CREB) to the transcription factor ZFHX3 (also known as ATBF1), which in turn promotes survival of neurons by inducing expression of platelet-derived growth factor receptor β (PDGFRB) is reported.
Journal ArticleDOI
Phosphorylation of the Cryptochrome 1 C-terminal Tail Regulates Circadian Period Length *
Peng Gao,Seung Hee Yoo,Kyung Jong Lee,Clark Rosensweig,Joseph S. Takahashi,Benjamin P C Chen,Carla B. Green +6 more
TL;DR: Phosphorylation of CRY1 on Ser-588 increases its half-life and lengthens the circadian period and is found to be robustly rhythmic in mouse liver nuclei and contributes to the proper circadian period length.
Journal ArticleDOI
Talking to chromatin: post-translational modulation of polycomb group function
TL;DR: Current insights in covalent modification of Polycomb Group proteins in the context of protein function are reviewed and a tentative view of integrated signaling to chromatin in thecontext of phosphorylation is presented.
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.