Article
Medicine, Research & Experimental
Le Zhang, Matthias Wirth, Upayan Patra, Jacob Stroh, Konstandina Isaakidis, Leonie Rieger, Susanne Kossatz, Maja Milanovic, Chuanbing Zang, Uta Demel, Jan Keiten-Schmitz, Kristina Wagner, Katja Steiger, Roland Rad, Florian Bassermann, Stefan Mueller, Ulrich Keller, Markus Schick
Summary: The DNA damage response (DDR) acts as a barrier to malignant transformation and is often impaired during tumorigenesis. We identified SLF2 as a regulator of the DDR and a biomarker for adverse prognosis in B-cell lymphoma (BCL) patients. SLF2 deficiency leads to loss of DDR factors and impairs CHK1 activation, and its genetic deletion drives lymphomagenesis in vivo. Tumor cells lacking SLF2 have high DNA damage levels and alterations in the post-translational SUMOylation pathway, making them sensitive to a clinically applicable SUMOylation inhibitor (SUMOi) and synergistic with DDR pathway inhibitors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Nareg Pinarbasi-Degirmenci, Ilknur Sur-Erdem, Vuslat Akcay, Yasemin Bolukbasi, Ugur Selek, Ihsan Solaroglu, Tugba Bagci-Onder
Summary: By applying fractionated radiotherapy over a long time and selecting irradiation-survivor glioblastoma cells, clinically relevant irradiation-exposed models were generated. The cells exhibited slower growth, resistance to secondary irradiation, upregulation of DDR-related genes, and better DNA repair capacity. The utility of combining DDR inhibitors and irradiation was demonstrated for both naive and IR-Surv glioblastoma cells, as long as cells are refrained from hypoxic conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jin Cai, Ningchao Wang, Guanglan Lin, Haowei Zhang, Weidong Xie, Yaou Zhang, Naihan Xu
Summary: RNA-binding protein MBNL2 plays a crucial role in regulating tumor cell proliferation and DNA damage response by modulating the PI3K/AKT pathway and affecting the expression of p21. Depletion of MBNL2 leads to increased phosphorylation levels of Chk1 and influences DNA damage response, ultimately altering tumor cell fate by inhibiting DNA damage repair and promoting DNA damage-induced apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Benyu Su, David Lim, Chenyang Qi, Zhongwei Zhang, Junxiao Wang, Fengmei Zhang, Chao Dong, Zhihui Feng
Summary: Cell cycle checkpoint kinases play a crucial role in protecting against replicative stress. Valproic acid (VPA), a histone deacetylase inhibitor, was found to promote breast cancer cell progression into G2/M phase while protecting normal cells by regulating PPP2R2A and Chk1 phosphorylation. The expression levels of PPP2R2A and pChk1 were also associated with patient survival.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Fiifi Neizer-Ashun, Resham Bhattacharya
Summary: The DNA damage response relies on CHK1 kinase for maintaining genomic integrity, involving in processes such as DNA replication and mitotic progression. While CHK1 has potential in cancer therapy, it has yet to be fully realized clinically.
Article
Virology
Lydia E. Hainley, Martina S. Hughson, Amithi Narendran, Ralph Smith, Justin Arthur, Alida Hayner-Buchan, David J. Conti, John M. Lehman, Thomas D. Friedrich
Summary: The BK polyomavirus, latent in the kidneys of most adults, can be reactivated in immunosuppressed states like after renal transplantation, leading to potential kidney damage. Reduction of immunosuppression has been effective in limiting BKPyV infection, but antiviral drugs are needed for better treatment. In this study, inhibition of the host DNA damage response was explored as a potential antiviral strategy, showing promising results in reducing BKPyV replication.
Article
Oncology
Nicola Lockwood, Silvia Martini, Ainara Lopez-Pardo, Katharina Deiss, Hendrika A. Segeren, Robert K. Semple, Ian Collins, Dimitra Repana, Mathias Cobbaut, Tanya Soliman, Francesca Ciccarelli, Peter J. Parker
Summary: G2 arrest is crucial for the faithful segregation of sister chromatids, and the p53-p21 signaling pathway plays an essential role in cell lines, patient-derived cells, and colorectal cancer organoids. In arrest-defective hTERT-positive cells, the PKC epsilon failsafe mechanism is engaged. In ALT-dependent cancer cells, a distinct form of p53-independent G2 arrest is mediated by BLM and Chk1.
Article
Oncology
Marta Llaurado Fernandez, E. Marielle Hijmans, Annemiek M. C. Gennissen, Nelson K. Y. Wong, Shang Li, G. Bea A. Wisman, Aleksandra Hamilton, Joshua Hoenisch, Amy Dawson, Cheng -Han Lee, Madison Bittner, Hannah Kim, Gabriel E. DiMattia, Christianne A. R. Lok, Cor Lieftink, Roderick L. Beijersbergen, Steven de Jong, Mark S. Carey, Rene Bernards, Katrien Berns
Summary: In Low-grade serous ovarian cancer (LGSOC), targeting specific genes can reverse resistance to MEKi. Combining pan-RAF inhibitors with MEKi shows promise in treating LGSOC and reduces proliferation of resistant cells.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Endocrinology & Metabolism
Yoshiko Matsumoto Ikushima, Motoharu Awazawa, Naoki Kobayashi, Sho Osonoi, Seiichi Takemiya, Hiroshi Kobayashi, Hirotsugu Suwanai, Yuichi Morimoto, Kotaro Soeda, Jun Adachi, Masafumi Muratani, Jean Charron, Hiroki Mizukami, Noriko Takahashi, Kohjiro Ueki
Summary: Research has shown that decreased phosphorylation of ERK1/2 in diabetes pathology leads to beta-cell dysfunction and hyperglycemia. Abrogation of ERK signaling in pancreatic beta-cells through deletion of Mek1 and Mek2 results in insufficient insulin production, reduced beta-cell proliferation, and decreased insulin exocytosis events in individual beta-cells.
Article
Cell Biology
Petra Haag, Magnus Olsson, Jeremy Forsberg, Marita Lagergren Lindberg, Bo Stenerlow, Dali Zong, Lena Kanter, Rolf Lewensohn, Kristina Viktorsson, Boris Zhivotovsky, Leif Stenke
Summary: This study demonstrates that the antibody conjugate Gemtuzumab ozogamicin (GO) induces apoptosis in human acute myeloid leukemia (AML) cells by triggering caspase-2 cleavage. These findings may have important clinical implications.
CELL DEATH DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Wonyoung Choi, Eun Sook Lee
Summary: The DNA damage response (DDR) pathway plays a critical role in maintaining genome stability and defects in this pathway are associated with cancer. Exploiting vulnerabilities in this pathway has led to successful anticancer therapies, such as PARP inhibitors. This review discusses key elements of the DDR pathway and the development of pharmacologic inhibitors. It also highlights the importance of biomarker studies and combination strategies in optimizing clinical benefits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chao Dong, Liwei An, Cheng-han Yu, Michael S. Y. Huen
Summary: The DYRK1B kinase plays a crucial role in maintaining rDNA stability, nucleolar reorganization, and inhibition of rRNA synthesis. Inhibition of DYRK1B results in sustained nucleolar transcription, hypersensitivity to DSBs at rDNA arrays, and requirement for DSB repair and rDNA copy number maintenance. These findings highlight the importance of DYRK1B as a key signaling intermediate in coordinating DSB repair and rDNA transcriptional activities within the nucleolus.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Plant Sciences
Leiyang Guo, Zhen Dong, Xiaolin Zhang, Yuanmiao Yang, Xiaosong Hu, Yacong Ji, Chongyang Li, Sicheng Wan, Jie Xu, Chaolong Liu, Yanli Zhang, Lichao Liu, Yaqiong Shi, Zonghui Wu, Yaling Liu, Hongjuan Cui
Summary: In this study, the researchers investigated the anti-tumor effect of a flavonoid called morusinol on melanoma cells. They found that morusinol could inhibit cell proliferation, induce cell cycle arrest and apoptosis, and cause DNA damage in melanoma cells. Furthermore, they discovered that morusinol could degrade CHK1 protein through the ubiquitin-proteasome pathway, leading to cell cycle arrest, apoptosis, and DNA damage response. These findings suggest that morusinol has the potential to be a candidate drug for the treatment of melanoma.
Article
Oncology
Oren Yakovian, Julia Sajman, Rand Arafeh, Yair Neve-Oz, Michal Alon, Yardena Samuels, Eilon Sherman
Summary: The study reveals the nanoscale organization and signal coupling of NRas and BRAF in melanoma cells, showing that mutant NRas exhibits more pronounced self-clustering and increased association with BRAF. The findings suggest a new regulatory mechanism for NRas signaling and potential therapeutic targets for MEK inhibitors in melanoma.
Article
Biochemistry & Molecular Biology
Linke Tang, Weifeng Yuan, Shitao Li, Xiuyan Ding, Liqian Zhu
Summary: In this study, the interaction between UV-primed global DDR and BoHV-1 productive infection was demonstrated. UV-primed global DDR differentially modulated the transcription of virus genes and stabilization of virus protein. Vice versa, the virus infection may affect UV-primed DDR signaling.
Article
Multidisciplinary Sciences
Mamie Yu, Suresh K. Selvaraj, May M. Y. Liang-Chu, Sahar Aghajani, Matthew Busse, Jean Yuan, Genee Lee, Franklin Peale, Christiaan Klijn, Richard Bourgon, Joshua S. Kaminker, Richard M. Neve
Article
Medicine, Research & Experimental
Rinske Drost, Kiranjit K. Dhillon, Hanneke van der Gulden, Ingrid van der Heijden, Inger Brandsma, Cristina Cruz, Dafni Chondronasiou, Marta Castroviejo-Bermejo, Ute Boon, Eva Schut, Eline van der Burg, Ellen Wientjens, Mark Pieterse, Christiaan Klijn, Sjoerd Klarenbeek, Fabricio Loayza-Puch, Ran Elkon, Liesbeth van Deemter, Sven Rottenberg, Marieke van de Ven, Dick H. W. Dekkers, Jeroen A. A. Demmers, Dik C. van Gent, Reuven Agami, Judith Balmana, Violeta Serra, Toshiyasu Taniguchi, Peter Bouwman, Jos Jonkers
JOURNAL OF CLINICAL INVESTIGATION
(2016)
Article
Cell Biology
Leonard D. Goldstein, James Lee, Florian Gnad, Christiaan Klijn, Annalisa Schaub, Jens Reeder, Anneleen Daemen, Corey E. Bakalarski, Thomas Holcomb, David S. Shames, Ryan J. Hartmaier, Juliann Chmielecki, Somasekar Seshagiri, Robert Gentleman, David Stokoe
Article
Cell Biology
Manuel Viotti, Catherine Wilson, Mark McCleland, Hartmut Koeppen, Benjamin Haley, Suchit Jhunjhunwala, Christiaan Klijn, Zora Modrusan, David Arnott, Marie Classon, Jean-Philippe Stephan, Ira Mellman
JOURNAL OF CELL BIOLOGY
(2018)
Article
Genetics & Heredity
Sjors M. Kas, Julian R. de Ruiter, Koen Schipper, Stefano Annunziato, Eva Schut, Sjoerd Klarenbeek, Anne Paulien Drenth, Eline van der Burg, Christiaan Klijn, Jelle J. ten Hoeve, David J. Adams, Marco J. Koudijs, Jelle Wesseling, Micha Nethe, Lodewyk F. A. Wessels, Jos Jonkers
Article
Biotechnology & Applied Microbiology
Christiaan Klijn, Steffen Durinck, Eric W. Stawiski, Peter M. Haverty, Zhaoshi Jiang, Hanbin Liu, Jeremiah Degenhardt, Oleg Mayba, Florian Gnad, Jinfeng Liu, Gregoire Pau, Jens Reeder, Yi Cao, Kiran Mukhyala, Suresh K. Selvaraj, Mamie Yu, Gregory J. Zynda, Matthew J. Brauer, Thomas D. Wu, Robert C. Gentleman, Gerard Manning, Robert L. Yauch, Richard Bourgon, David Stokoe, Zora Modrusan, Richard M. Neve, Frederic J. de Sauvage, Jeffrey Settleman, Somasekar Seshagiri, Zemin Zhang
NATURE BIOTECHNOLOGY
(2015)
Article
Multidisciplinary Sciences
Christiaan Klijn, Marco J. Koudijs, Jaap Kool, Jelle ten Hoeve, Mandy Boer, Joost de Moes, Waseem Akhtar, Martine van Miltenburg, Annabel Vendel-Zwaagstra, Marcel J. T. Reinders, David J. Adams, Maarten van Lohuizen, John Hilkens, Lodewyk F. A. Wessels, Jos Jonkers
Article
Multidisciplinary Sciences
Marieke A. Vollebergh, Christiaan Klijn, Philip C. Schouten, Jelle Wesseling, Danielle Israeli, Bauke Ylstra, Lodewyk F. A. Wessels, Jos Jonkers, Sabine C. Linn
Article
Multidisciplinary Sciences
Christian Bowman-Colin, Bing Xia, Samuel Bunting, Christiaan Klijn, Rinske Drost, Peter Bouwman, Laura Fineman, Xixi Chen, Aedin C. Culhane, Hong Cai, Scott J. Rodig, Roderick T. Bronson, Jos Jonkers, Andre Nussenzweig, Chryssa Kanellopoulou, David M. Livingston
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Biochemistry & Molecular Biology
Thijs J. Hagenbeek, Joshua D. Webster, Noelyn M. Kljavin, Matthew T. Chang, Trang Pham, Ho-June Lee, Christiaan Klijn, Allen G. Cai, Klara Totpal, Buvana Ravishankar, Naiying Yang, Da-Hye Lee, Kevin B. Walsh, Georgia Hatzivassiliou, Cecile C. de la Cruz, Stephen E. Gould, Xiumin Wu, Wyne P. Lee, Shuqun Yang, Zhixiang Zhang, Qingyang Gu, Qunsheng Ji, Erica L. Jackson, Dae-Sik Lim, Anwesha Dey
Article
Multidisciplinary Sciences
Jinfeng Liu, Mark McCleland, Eric W. Stawiski, Florian Gnad, Oleg Mayba, Peter M. Haverty, Steffen Durinck, Ying-Jiun Chen, Christiaan Klijn, Suchit Jhunjhunwala, Michael Lawrence, Hanbin Liu, Yinan Wan, Vivek Chopra, Murat B. Yaylaoglu, Wenlin Yuan, Connie Ha, Houston N. Gilbert, Jens Reeder, Gregoire Pau, Jeremy Stinson, Howard M. Stern, Gerard Manning, Thomas D. Wu, Richard M. Neve, Frederic J. de Sauvage, Zora Modrusan, Somasekar Seshagiri, Ron Firestein, Zemin Zhang
NATURE COMMUNICATIONS
(2014)
Article
Oncology
Ivana Yen, Frances Shanahan, Mark Merchant, Christine Orr, Thomas Hunsaker, Matthew Durk, Hank La, Xiaolin Zhang, Scott E. Martin, Eva Lin, John Chan, Yihong Yu, Dhara Amin, Richard M. Neve, Amy Gustafson, Avinashnarayan Venkatanarayan, Scott A. Foster, Joachim Rudolph, Christiaan Klijn, Shiva Malek
Article
Oncology
Robert Piskol, Ling Huw, Ismail Sergin, Christiaan Kljin, Zora Modrusan, Doris Kim, Noelyn Kljavin, Rachel Tam, Rajesh Patel, Jeremy Burton, Elicia Penuel, Xueping Qu, Hartmut Koeppen, Teiko Sumiyoshi, Frederic de Sauvage, Mark R. Lackner, Felipe de Sousa e Melo, Omar Kabbarah
CLINICAL CANCER RESEARCH
(2019)
Article
Oncology
Steffan Vartanian, James Lee, Christiaan Klijn, Florian Gnad, Maria Bagniewska, Gabriele Schaefer, Donglu Zhang, Jenille Tan, Sara A. Watson, Liling Liu, Honglin Chen, Yuxin Liang, Colin Watanabe, Trinna Cuellar, David Kan, Ryan J. Hartmaier, Ted Lau, Michael R. Costa, Scott E. Martin, Mark Merchant, Benjamin Haley, David Stokoe