Article
Multidisciplinary Sciences
Zachary T. Spencer, Victoria H. Ng, Hassina Benchabane, Ghalia Saad Siddiqui, Deepesh Duwadi, Ben Maines, Jamal M. Bryant, Anna Schwarzkopf, Kai Yuan, Sara N. Kassel, Anant Mishra, Ashley Pimentel, Andres M. Lebensohn, Rajat Rohatgi, Scott A. Gerber, David J. Robbins, Ethan Lee, Yashi Ahmed
Summary: The stabilization of the Wnt receptor Arrow/LRP6 by the Usp46-Uaf1-Wdr20 deubiquitylase complex enhances the sensitivity of target cells to the Wingless morphogen, leading to precise signaling in the Wnt morphogen gradient.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Martina Tufano, Laura Marrone, Chiara D'Ambrosio, Valeria Di Giacomo, Simona Urzini, Yichuan Xiao, Monica Matuozzo, Andrea Scaloni, Maria Fiammetta Romano, Simona Romano
Summary: FKBP51 is crucial for the survival of cancer cells, especially melanoma. It involved in various signaling pathways and forms a complex with Akt and PHLPP, known for dephosphorylation of Akt. This study focuses on the regulation of Akt activation by canonical and spliced isoforms of FKBP51. The TPR domain of FKBP51 is found to mediate Akt ubiquitination at K63, an important step for Akt activation. Surprisingly, PHLPP does not promote Akt phosphorylation when silenced and even induces Akt phosphorylation when overexpressed. PHLPP stabilizes TRAF6, an E3 ubiquitin ligase, and supports K63-ubiquitination of Akt. The interactome profile of FKBP51 in melanoma cells emphasizes the crucial role of PHLPP in enhancing oncogenic characteristics, particularly cell proliferation.
CELL DEATH & DISEASE
(2023)
Article
Hematology
Fraser Soares, Branson Chen, Jong Bok Lee, Musaddeque Ahmed, Dalam Ly, Enoch Tin, Hyeonjeong Kang, Yong Zeng, Nayeema Akhtar, Mark D. Minden, Housheng Hansen He, Li Zhang
Summary: AMl remains a devastating disease for which new therapies are needed. Targeted adoptive T-cell therapies have shown promise in some leukemias but not in AML. A study utilizing CRISPR/Cas9 screens identified SAGA and CD64 as key factors influencing the sensitivity of AML cells to DNT therapy.
Article
Oncology
Naizhi Sun, Jiacheng Shen, Yuhua Shi, Biao Liu, Shengguo Gao, Yichuan Chen, Jinwei Sun
Summary: This study aimed to investigate the molecular mechanisms of TRIM58 in colorectal cancer (CRC) development. TRIM58 is an E3 ubiquitin ligase and a potential prognostic marker for cancer. The study found that TRIM58 acts as a tumor suppressor in CRC by promoting RECQL4 ubiquitination and inhibiting the AKT signaling pathway, suggesting it could be a potential target for CRC treatment.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Deng-Ke Li, Xing-Rui Chen, Li-Na Wang, Jia-Hong Wang, Yue-Ting Wen, Zi-Ying Zhou, Ji-Ke Li, Jing-Xian Liu, Lin-Bo Cai, Shui-Sheng Zhong, Xiao-Ming Lyu, Faleti Oluwasijibomi Damola, Min-Ying Li, Jing-Jing Zhang, Yu-Mei Zeng, Qian-Li Wang, Qian-Bing Zhang, Hao Lyu, Xiao-Yan Fu, Wei Wang, Xin Li, Zhong-Xi Huang, Kai-Tai Yao
Summary: This study reveals the association between EBV and LN metastasis in NPC and demonstrates that EBV infection promotes cancer-associated lymphangiogenesis and LN metastasis. By regulating PHLPP1/p-AKT/HIF1a/VEGF-C, EBV induces lymphangiogenesis in NPC, providing a new therapeutic target for NPC with lymphatic metastasis.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Chan Wang, Jiaxin Chen, Yeye Kuang, Xiaoqing Cheng, Min Deng, Zhinong Jiang, Xiaotong Hu
Summary: The study found that TRPM4 is a novel methylated tumor suppressor gene that is downregulated in colorectal cancer. TRPM4 activates calpain-mediated cleavage of FAK through modulating the PI3K/Akt/mTOR signaling cascade, thereby impeding CRC migration and invasion.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Yueshuo Li, Feng Shi, Jianmin Hu, Longlong Xie, Lin Zhao, Min Tang, Xiangjian Luo, Mao Ye, Hui Zheng, Min Zhou, Na Liu, Ann M. Bode, Jia Fan, Jian Zhou, Qiang Gao, Shuangjian Qiu, Weizhong Wu, Xin Zhang, Weihua Liao, Ya Cao
Summary: In this study, CYLD was identified as a deubiquitinase for p18, stabilizing the protein and regulating the G1/S transition. Restoring CYLD can prevent EBV-induced viral replication and tumor growth. The reconstitution of the CYLD-p18 axis may be a promising approach for EBV-positive cancer therapy.
NPJ PRECISION ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M. Ittmann, Chad J. Creighton, Yingnan Bian, Yanling Meng, David R. Rowley, Peter S. Nelson, David D. Moore, Feng Yang
Summary: The study revealed that MAPK4 promotes prostate cancer growth and castration resistance by activating GATA2/AR and AKT pathways. Activation of both GATA2/AR and AKT is necessary for MAPK4 tumor-promoting activity.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Fan Wu, Jin He, Qianxi Deng, Jun Chen, Mingyu Peng, Jiayi Xiao, Yiwei Zeng, Lin Yi, Zhuoqing Li, Rui Tian, Zheng Jiang
Summary: This study investigates the role of neuro-globin (NGB) as a tumor suppressor gene in pancreatic cancer. Analysis of the TCGA and GTEx public datasets reveals that NGB expression is commonly downregulated in pancreatic cancer cells and tissues, and this correlates with patient age and prognosis. Experimental results show that NGB inhibits pancreatic cancer progression by inducing cell cycle arrest, apoptosis, inhibiting migration and invasion, reversing the EMT process, and suppressing cell proliferation and development. Further analysis and experiments confirm that NGB inhibits the EGFR/AKT/ERK pathway by binding to and reducing the expression of GNAI1 and p-EGFR.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Hematology
Mingyang Li, Xuan Wang, Enli Yang, Yiming Li, Yiming Geng, Zhanwei Chen, Shengyun Huang, Dongsheng Zhang, Haiwei Wu
Summary: This study found that the expression of deubiquitylase OTUB1 was significantly increased in infantile hemangioma (IH) and it promoted angiogenesis by regulating glycolysis. OTUB1 was shown to interact with and deubiquitylate TGFBI, leading to the progression of IH. These findings suggest that targeting OTUB1 may be a potential therapeutic strategy for inhibiting IH progression and tumor angiogenesis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Oncology
Wei Wang, Xinhang Xia, Kuifei Chen, Meng Chen, Yinnan Meng, Dongqing Lv, Haihua Yang
Summary: PHLPP, a potential tumor suppressor, is found to be a key regulator of sensitivity to EGFR-TKIs in NSCLC. Loss of PHLPP function leads to activation of survival pathways, reducing sensitivity to EGFR-TKIs. Enhancing PHLPP expression may be a valuable strategy for delaying or overcoming EGFR-TKIs drug resistance.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kimia Mirzakhani, Julia Kallenbach, Seyed Mohammad Mahdi Rasa, Federico Ribaudo, Martin Ungelenk, Marzieh Ehsani, Wenrong Gong, Nikolaus Gassler, Mirjam Leeder, Marc-Oliver Grimm, Francesco Neri, Aria Baniahmad
Summary: The study identified that supraphysiological androgen levels induce cellular senescence in prostate cancer cells through the activation of p15(INK4b) and AKT phosphorylation, with lncRNASAT1 playing a crucial regulatory role. This novel AR-lncRNASAT1-AKT-p15(INK4b) signaling axis mediates supraphysiological androgen-induced cellular senescence.
Article
Cell Biology
Medha Sharma, Chinmoy Sankar Dey
Summary: The study determines the role of individual PHLPP isoforms in insulin signaling and insulin resistance in neuronal cells. The results show that overexpressed and elevated endogenous expression of PHLPP isoforms under insulin resistant condition affect neuronal glucose uptake, while silencing Scribble increases glucose uptake.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Cell Biology
Zhipeng Xu, Min Liu, Jin Wang, Kai Liu, Liuyu Xu, Demin Fan, Hui Zhang, Wenxin Hu, Dan Wei, Jianning Wang
Summary: The MYH9 gene is commonly upregulated in clear cell renal cell carcinoma (ccRCC) and its overexpression predicts poor prognosis. Knockdown of MYH9 inhibits the proliferative and metastatic potentials of ccRCC cells, while overexpression enhances these properties. Furthermore, MYH9 plays vital roles through the AKT signaling pathway and determines the response of ccRCC cells to sunitinib treatment.
CELL DEATH DISCOVERY
(2022)
Review
Biotechnology & Applied Microbiology
Xian-Wen Liang, Sheng-Zhong Wang, Bing Liu, Jia-Cheng Chen, Zhi Cao, Feng-Ran Chu, Xiong Lin, Hui Liu, Jin-Cai Wu
Summary: Ubiquitin is a small protein that can be added onto target protein to induce degradation and modulate the activity and stability of the protein. Deubiquitinases (DUBs) are a class of enzymes that can remove ubiquitin from substrate proteins, providing positive regulation at the transcriptional level, post-translational modification, protein interaction, etc. The reversible and dynamic process of ubiquitination-deubiquitination plays a critical role in maintaining protein homeostasis and is essential for almost all biological processes.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)