Article
Multidisciplinary Sciences
Trisha A. Macrae, Miguel Ramalho-Santos
Summary: The study reveals a regulatory axis between the deubiquitinase Usp9x and PRC2 that is critical for self-renewal of mouse embryonic stem cells. Different levels of Usp9x lead to distinct chromatin and transcriptional patterns in ES cells, reminiscent of different developmental stages. Deletion of Usp9x in post-implantation embryos results in derepression of genes and morphological abnormalities, suggesting a crucial role of Usp9x-PRC2 axis in development.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Juan M. Roldan-Romero, Carlos Valdivia, Maria Santos, Javier Lanillos, Pablo Maroto, Georgia Anguera, Bruna Calsina, Angel Martinez-Montes, Maria Monteagudo, Sara Mellid, Luis J. Leandro-Garcia, Cristina Montero-Conde, Alberto Cascon, Giovanna Roncador, Javier Coloma, Mercedes Robledo, Cristina Rodriguez-Antona
Summary: Mammalian target of rapamycin (mTOR) is an attractive target for cancer therapy due to its role in promoting tumor growth and resistance to chemotherapy. Whole exome sequencing of chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed somatic mutations in the deubiquitinase gene USP9X. By studying multiple patients' samples, it was confirmed that USP9X plays a role in sensitivity to mTOR inhibitors by affecting autophagy and the p62 pathway. These findings suggest that USP9X could serve as a potential marker and strategy for increasing sensitivity to mTOR inhibitors in chRCC patients.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Jiewei Wang, Yiping Dong, Huailu Ma, Lingzhi Wu, Xinghua Zhen, Lichun Tang, Jianping Jin, Suxia Han, Pumin Zhang, Jin Peng
Summary: The study shows that USP28 is a key regulator of TNBC cell proliferation and its inhibitor exhibits anti-tumor activity against xenografts derived from TNBC cells, suggesting that USP28 could be a potential therapeutic target for triple negative breast cancer.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Fei Xu, Jiajia Li, Mengdong Ni, Jingyi Cheng, Haiyun Zhao, Shanshan Wang, Xiang Zhou, Xiaohua Wu
Summary: The study revealed that FBW7 suppresses tumor growth and progression in ovarian cancer by antagonizing YTHDF2-mediated BMF mRNA decay. This highlights the importance of the FBW7-YTHDF2 regulatory axis in ovarian cancer development and suggests potential therapeutic targets for the treatment of this disease.
Article
Oncology
Sophia A. Hogh-Binder, Diana Klein, Frederik Wolfsperger, Stephan M. Huber, Joerg Hennenlotter, Arnulf Stenzl, Justine Rudner
Summary: Radiotherapy is an important treatment option for prostate cancer, but cancer cells often develop resistance, limiting its effectiveness. The Bcl-2 protein family plays a role in regulating sensitivity to radiotherapy. In this study, we found that the levels of USP9x and Mcl-1 increased during prostate cancer progression. Blocking Mcl-1 or USP9x improved the response of prostate cancer cells to radiotherapy. Additionally, radiotherapy itself affected the stability of Mcl-1 protein in prostate cancer cells.
Article
Biochemistry & Molecular Biology
Zeng Ye, Qifeng Zhuo, Qiangsheng Hu, Xiaowu Xu, Mengqi Liu, Zheng Zhang, Wenyan Xu, Wensheng Liu, Guixiong Fan, Yi Qin, Xianjun Yu, Shunrong Ji
Summary: FBW7 acts as a tumor suppressor by targeting oncoproteins for degradation in pancreatic cancer, with decreased expression leading to destabilization and activation of pathways like ferroptosis and apoptosis which inhibit tumor growth, suggesting potential new strategies for comprehensive treatment of pancreatic cancer.
Article
Multidisciplinary Sciences
Oxana Dmitrieva-Posocco, Andrea C. Wong, Patrick Lundgren, Aleksandra M. Golos, Helene C. Descamps, Lenka Dohnalova, Zvi Cramer, Yuhua Tian, Brian Yueh, Onur Eskiocak, Gabor Egervari, Yemin Lan, Jinping Liu, Jiaxin Fan, Jihee Kim, Bhoomi Madhu, Kai Markus Schneider, Svetlana Khoziainova, Natalia Andreeva, Qiaohong Wang, Ning Li, Emma E. Furth, Will Bailis, Judith R. Kelsen, Kathryn E. Hamilton, Klaus H. Kaestner, Shelley L. Berger, Jonathan A. Epstein, Rajan Jain, Mingyao Li, Semir Beyaz, Christopher J. Lengner, Bryson W. Katona, Sergei I. Grivennikov, Christoph A. Thaiss, Maayan Levy
Summary: The study identifies a metabolite signalling pathway that can be used as a strategy for preventing and treating colorectal cancer. Ketogenic diets and the ketone body BHB show a strong inhibitory effect on tumor growth by reducing cell proliferation. The findings suggest that BHB-triggered pathway could play a crucial role in regulating intestinal tumorigenesis.
Article
Oncology
Shan Wang, Xiaofang Huo, Yiping Yang, Yingxi Mo, Rahul K. Kollipara, Ralf Kittler
Summary: The deubiquitinase USP9X stabilizes EWS-FLI1 protein expression in Ewing sarcoma, and its inhibitor WP1130 can rapidly degrade EWS-FLI1 and inhibit the growth of Ewing sarcoma cells and tumors.
Article
Oncology
Wentao Liu, Dianyun Ren, Wei Xiong, Xin Jin, Liang Zhu
Summary: Our study identified that NFAT1, when overexpressed in RCC, was associated with poor prognosis and could enhance tumor growth by increasing PD-L1 expression. Additionally, NFAT1 was found to be stabilized in sunitinib-resistant RCC through hyperactivation of the PI3K/AKT/GSK-3 beta signaling pathway. The downregulation of FBW7, which promotes NFAT1 degradation, was induced by FOXA1 and SETD2 in sunitinib-resistant RCC, contributing to immune response modulation. This study reveals a new role for the FBW7/NFAT1 axis in RCC response to TKIs and ICIs, suggesting NFAT1 as a potential therapeutic target for RCC treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Cristina Corno, Padraig D'Arcy, Marina Bagnoli, Biagio Paolini, Matteo Costantino, Nives Carenini, Elisabetta Corna, Paola Alberti, Delia Mezzanzanica, Diego Colombo, Stig Linder, Noemi Arrighetti, Paola Perego
Summary: This study identified the increased activity of ubiquitin protease USP8 in cisplatin-resistant cells and demonstrated that silencing of USP8 decreased cancer cell survival and increased sensitivity to cisplatin. Immunohistochemical analysis of clinical specimens indicated that USP8 positivity is associated with adverse prognosis in advanced stage ovarian carcinoma. Therefore, USP8 may serve as a diagnostic marker and therapeutic target to improve the efficacy of platinum-based therapy in ovarian carcinoma.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shuyu Yu, Weicheng Zang, Yuchong Qiu, Liming Liao, Xiaofeng Zheng
Summary: Aberrant regulation of ubiquitination can lead to metabolic reprogramming in tumor cells. OTUB2, an OTU deubiquitinase, is upregulated in colorectal cancer and exacerbates its progression by modulating aerobic glycolysis. Depletion of OTUB2 reduces glucose consumption, lactate production, and cellular ATP production, as well as sensitizing CRC cells to chemotherapy drugs.
Article
Pharmacology & Pharmacy
Ruohan Zhang, Serra Ozgen, Hongke Luo, Judith Krigman, Yutong Zhao, Gang Xin, Nuo Sun
Summary: In this study, the researchers investigate the role of Parkin and USP30 in regulating the AKT/mTOR signaling during mitophagy. They found that Parkin inhibits AKT/mTOR signaling, while USP30 antagonizes the activity of Parkin to sustain AKT/mTOR activity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Diana Campos-Iglesias, Julia M. Fraile, Gabriel Bretones, Alejandro A. Montero, Elena Bonzon-Kulichenko, Jesus Vazquez, Carlos Lopez-Otin, Jose M. P. Freije
Summary: USP49 deubiquitinase is identified as a novel regulator of the spindle checkpoint. Loss of USP49 impairs proliferation and increases aneuploidy in cancer cell lines. USP49-depleted cells can overcome SAC-induced arrest in presence of nocodazole.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Tangming Guan, Xiao Yang, Hui Liang, Jiayi Chen, Yan Chen, Yingjie Zhu, Tongzheng Liu
Summary: This study reveals the important regulatory mechanism of breast cancer metastasis and chemoresistance, namely the USP9X-Snail1 axis, and provides a rationale for potential therapeutic interventions in the treatment of TNBC.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jia Song, Yuning Zhang, Yunyang Bai, Xiaowen Sun, Yanhui Lu, Yusi Guo, Ying He, Min Gao, Xiaopei Chi, Boon Chin Heng, Xin Zhang, Wenjing Li, Mingming Xu, Yan Wei, Fuping You, Xuehui Zhang, Dan Lu, Xuliang Deng
Summary: A subset of neutrophils that secrete pro-inflammatory cytokines and have enhanced migratory capacity is found to be related to periodontal pathogenesis. The protein OTUD1 is identified as a regulator in the polarization of these secretory neutrophils.
Article
Biochemistry & Molecular Biology
Sarah J. Tarr, Chrislaine Withers-Martinez, Helen R. Flynn, Ambrosius P. Snijders, Laura Masino, Konstantinos Koussis, David J. Conway, Michael J. Blackman
BIOCHEMICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Souradeep Basu, Emma L. Roberts, Andrew W. Jones, Matthew P. Swaffer, Ambrosius P. Snijders, Paul Nurse
Article
Cell Biology
Marta Budzinska, David Villarroel-Campos, Matthew Golding, Anne Weston, Lucy Collinson, Ambrosius P. Snijders, Giampietro Schiavo
JOURNAL OF CELL SCIENCE
(2020)
Article
Multidisciplinary Sciences
Sandipan Ray, Utham K. Valekunja, Alessandra Stangherlin, Steven A. Howell, Ambrosius P. Snijders, Gopinath Damodaran, Akhilesh B. Reddy
Article
Multidisciplinary Sciences
Morgan Jones, Fabienne Beuron, Aaron Borg, Andrea Nans, Christopher P. Earl, David C. Briggs, Ambrosius P. Snijders, Maureen Bowles, Edward P. Morris, Mark Linch, Neil Q. McDonald
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Daniel Fisch, Barbara Clough, Marie-Charlotte Domart, Vesela Encheva, Hironori Bando, Ambrosius P. Snijders, Lucy M. Collinson, Masahiro Yamamoto, Avinash R. Shenoy, Eva-Maria Frickel
Article
Microbiology
Judith L. Green, Yang Wu, Vesela Encheva, Edwin Lasonder, Adchara Prommaban, Simone Kunzelmann, Evangelos Christodoulou, Munira Grainger, Ngoc Truongvan, Sebastian Bothe, Vikram Sharma, Wei Song, Irene Pinzuti, Chairat Uthaipibull, Somdet Srichairatanakool, Veronique Birault, Gordon Langsley, Hermann Schindelin, Benjamin Stieglitz, Ambrosius P. Snijders, Anthony A. Holder
Article
Multidisciplinary Sciences
Gabriel Tarrason Risa, Fredrik Hurtig, Sian Bray, Anne E. Hafner, Lena Harker-Kirschneck, Peter Faull, Colin Davis, Dimitra Papatziamou, Delyan R. Mutavchiev, Catherine Fan, Leticia Meneguello, Andre Arashiro Pulschen, Gautam Dey, Sian Culley, Mairi Kilkenny, Diorge P. Souza, Luca Pellegrini, Robertus A. M. de Bruin, Ricardo Henriques, Ambrosius P. Snijders, Andela Saric, Ann-Christin Lindas, Nicholas P. Robinson, Buzz Baum
Article
Multidisciplinary Sciences
Uddalak Majumdar, Sathiyanarayanan Manivannan, Madhumita Basu, Yukie Ueyama, Mark C. Blaser, Emily Cameron, Michael R. McDermott, Joy Lincoln, Susan E. Cole, Stephen Wood, Elena Aikawa, Brenda Lilly, Vidu Garg
Summary: Nitric oxide regulates NOTCH pathway through S-nitrosylation to prevent calcific aortic valve disease.
Article
Multidisciplinary Sciences
Omar M. Khan, Jorge Almagro, Jessica K. Nelson, Stuart Horswell, Vesela Encheva, Kripa S. Keyan, Bruce E. Clurman, Ambrosius P. Snijders, Axel Behrens
Summary: The study demonstrates that TRIP12 mediates branched K11-linked ubiquitylation of FBW7, regulating its stability and the abundance of a subset of SCFFBW7 substrates, with concomitant FBW7 inactivation rescuing the effects of TRIP12 deficiency.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Stephen A. Wood, Peter G. Hains, Arnaud Muller, Melissa Hill, Susitha Premarathne, Mariyam Murtaza, Phillip J. Robinson, George D. Mellick, Alex M. Sykes
Summary: In this study, we quantified proteomic differences between healthy control and PD patient cells and identified the critical role of the unfolded protein response (UPR) in PD patients. PD patients with high amounts of PDIA6 and HYOU1 proteins were more sensitive to endoplasmic reticulum stress. These findings provide insight into underlying cellular dysfunctions in PD patients.
PROTEOMICS CLINICAL APPLICATIONS
(2022)
Article
Biochemistry & Molecular Biology
William Gang Miao, Thanh Nguyen, Jamila Iqbal, Gregory K. Pierens, Linlin Ma, Des R. Richardson, Stephen A. Wood, George D. Mellick, Ronald J. Quinn, Yunjiang Feng
Summary: This study evaluated the effects of natural compounds from Ligusticum chuanxiong on Parkinson's Disease (PD) cells, and found that 34 compounds strongly affected the staining of multiple cellular organelles, which are closely related to the pathogenesis of PD. The results helped rationalize the traditional use of Ligusticum chuanxiong in PD treatment, and these compounds can serve as chemical probes to study the molecular pathways of PD.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Oncology
Kripa S. Keyan, Rania Alanany, Amira Kohil, Omar M. Khan
Summary: The E3 ubiquitin ligase TRIP12 is required for efficient mitosis and completion of cell division in cancer cells. Inhibition of TRIP12 enhances Taxol-induced cell death, depending on the action of FBW7 and MCL-1. Therefore, the TRIP12/FBW7/MCL-1 axis plays a crucial role in the response of cancer cells to Taxol.
Article
Engineering, Environmental
Md Hafiz All Hosen, Alex M. M. Sykes, Stephen A. A. Wood, Frederic D. L. Leusch, Deanne J. J. Whitworth, Susan M. Bengtson M. Nash
Summary: Cetaceans are at risk of accumulating environmental contaminants due to their longevity and high body fat. However, there is a lack of specific chemical effect data for these species. Recent advances in cetacean cell culture have allowed for the application of toxicological effect assessment approaches.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Biochemical Research Methods
Andrew W. Jones, Helen R. Flynn, Frank Uhlmann, Ambrosius P. Snijders, Sandra A. Touati