Review
Biochemistry & Molecular Biology
Filipy Borghi, Adolfo Saiardi
Summary: This article reviews the synthesis and functions of inorganic polyphosphate (polyP) in microorganisms, proposes the evolutionary origin of polyP synthesis mechanism and the potential polyP physiology in the nucleus.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Cell Biology
Jingtai Zhi, Linfei Hu, Yuyang Qian, Ning Kang, Xinwei Yun, Xin Wang, Xianhui Ruan, Dongmei Huang, Weiwei Yang, Xiangrui Meng, Tianze Zhu, Wei Wang, Xiangqian Zheng
Summary: This study reveals the crucial role of Aurora-A in regulating energy supply in thyroid cancer cells, and highlights the potential of combining Alisertib with Sorafenib for treating advanced thyroid carcinoma.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Aziz M. Rangwala, Victoria R. Mingione, George Georghiou, Markus A. Seeliger
Summary: Phosphorylation plays a vital role in regulating biological processes, and protein kinases have been extensively studied for their involvement in human health and disease. Some kinases possess additional catalytic functions in addition to phosphotransferase activity, while others have lost their catalytic activity completely. In this study, we analyzed the UniProtKB database for bifunctional protein kinases and focused on those crucial for bacterial and human cellular homeostasis. These kinases have diverse functional roles in environmental sensing, metabolic regulation, immune-host defense, and cell cycle control. This article explores their dual catalytic activities and their contributions to disease pathogenesis.
Article
Microbiology
Bradley Benjamin, Angad Garg, Nikolaus Jork, Henning J. Jessen, Beate Schwer, Stewart Shuman
Summary: We studied the biochemical properties and mutations of the autonomous Asp1 kinase domain in fission yeast. The results showed that under optimal kinase conditions, the reaction of Asp1 kinase with IP6 and ATP resulted in both IP6 phosphorylation to 1-IP7 and hydrolysis of the ATP gamma-phosphate with near-equal partitioning between productive 1-IP7 synthesis and unproductive ATP hydrolysis.
Article
Multidisciplinary Sciences
Maria Angeles Marquez-Monino, Raquel Ortega-Garcia, Megan L. Shipton, Elsa Franco-Echevarria, Andrew M. Riley, Julia Sanz-Aparicio, Barry V. L. Potter, Beatriz Gonzalez
Summary: DDP1 is a Nudix enzyme that exhibits activity on various substrates, with the molecular basis for its activity and different substrate binding modes revealed in this study. The findings have implications for inositide research and inhibitor design.
Article
Biochemistry & Molecular Biology
Esther Riemer, Danye Qiu, Debabrata Laha, Robert K. Harmel, Philipp Gaugler, Verena Gaugler, Michael Frei, Mohammad-Reza Hajirezaei, Nargis Parvin Laha, Lukas Krusenbaum, Robin Schneider, Adolfo Saiardi, Dorothea Fiedler, Henning J. Jessen, Gabriel Schaaf, Ricardo F. H. Giehl
Summary: This study provides comprehensive insights into how inositol (pyro)phosphate metabolism is regulated by Pi and dependent on the inositol phosphate kinase ITPK1. The research demonstrates that inositol pyrophosphates are more responsive to Pi than lower inositol phosphates and can be separated in different isomers in plants. Additionally, the study identifies new regulatory inositol pyrophosphates and their synthesis with Pi-dependent changes in nutritional and energetic states.
Article
Endocrinology & Metabolism
Xiaozhe Zhang, Na Li, Jun Zhang, Yanshen Zhang, Xiaoli Yang, Yifan Luo, Bobo Zhang, Zhixue Xu, Zhenhua Zhu, Xiuyan Yang, Yuan Yan, Biao Lin, Shen Wang, Da Chen, Caichao Ye, Yan Ding, Mingliang Lou, Qingcui Wu, Zhanfeng Hou, Keren Zhang, Ziming Liang, Anqi Wei, Bianbian Wang, Changhe Wang, Nan Jiang, Wenqing Zhang, Guozhi Xiao, Cong Ma, Yan Ren, Xiangbing Qi, Weiping Han, Chao Wang, Feng Rao
Summary: The study demonstrates that 5-IP7 mediates parasympathetic stimulation-induced insulin release in beta cells by activating IP6K1 and triggering binding of Syt7 with Ca2+ ion. This mechanism proposes a new conceptual framework for inositol pyrophosphate physiology, highlighting the role of 5-IP7 as a GPCR second messenger in transmitting G(q)-coupled GPCR stimulation for insulin secretion.
Article
Chemistry, Analytical
Yao Xu, Mengmeng Zheng, Li Gong, Guizhen Liu, Shanshan Qian, Ying Han, Jingwu Kang
Summary: Profiling drug-protein interactions is crucial for understanding drug mechanisms and predicting potential side effects. This study proposes a strategy using multiple mass spectrometry-based omics analyses to comprehensively profile drug-protein interactions. The integration of chemoproteomics, phosphoproteomics, and untargeted metabolomics provides insights into the complex mechanism of action of rapamycin.
ANALYTICAL CHEMISTRY
(2023)
Article
Oncology
Mirko Minini, Alice Senni, Xingkang He, Sara Proietti, Domenico Liguoro, Angela Catizone, Alessandro Giuliani, Rita Mancini, Andrea Fuso, Alessandra Cucina, Yihai Cao, Mariano Bizzarri
Summary: Myo-Inositol inhibits the PI3K/Akt pathway, particularly effective in triple-negative breast cancer cells, but not in hormone-responsive breast cancer cells unless estrogen effects are counteracted. This novel axis involving miR-125a-5p downregulating IP(6)K1 gene could be activated as a molecular target therapy in breast cancer, inhibiting metastasis and tumor progression.
Article
Genetics & Heredity
Renfei Ma, Shangfu Li, Wenshuo Li, Lantian Yao, Hsien-Da Huang, Tzong-Yi Lee
Summary: The purpose of this work is to enhance the KinasePhos tool, which predicts kinase-specific phosphorylation sites using machine learning. Through collecting experimentally verified data, a total of 41,421 phosphorylation sites were identified, which cover 1380 unique kinases. Based on kinase classification, 771 predictive models were built, showing higher accuracy than other tools. The web interface of KinasePhos 3.0 has been redesigned to provide comprehensive annotations, and a downloadable prediction tool is available for large-scale phosphoproteomic data.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Cell Biology
Chunlan Xu, Kunao Yang, Zuodong Xuan, Jinxin Li, Yankuo Liu, Yue Zhao, Zeyuan Zheng, Yang Bai, Zhiyuan Shi, Chen Shao, Lei Zhang, Huimin Sun
Summary: BCKDK is overexpressed in breast cancer and is associated with malignancy and metastasis. It promotes directed migration of breast cancer cells by disrupting cell adhesion and extracellular matrix formation and regulates the ubiquitination of talin1 and the activation of the FAK/MAPK pathway. BCKDK may serve as a biomarker for breast cancer metastasis and contribute to the development of new diagnostic markers and therapies.
CELL DEATH & DISEASE
(2023)
Article
Endocrinology & Metabolism
Bing Zhou, Yunchen Luo, Nana Ji, Cheng Hu, Yan Lu
Summary: Alterations in hepatic lipid metabolism may contribute to the onset of non-alcoholic fatty liver disease. Zhou et al. identify orosomucoid 2 (ORM2) as a key regulator of lipid homeostasis in the liver. ORM2 activates the AMP-activated protein kinase signaling to inhibit lipogenesis. Additionally, injections of ORM2 protein improved liver steatosis and atherosclerosis.
Article
Microbiology
Paul Ramp, Christopher Pfleger, Jonas Dittrich, Christina Mack, Holger Gohlke, Michael Bott
Summary: myo-, scyllo-, and d-chiro-inositol are cyclic sugar alcohols with various biological functions and serve as carbon sources for microbes. Inositol dehydrogenases (IDHs) catalyze the oxidation of inositol and initiate its catabolism. Corynebacterium glutamicum encodes seven potential IDHs, and this study identified four of them as key enzymes involved in inositol catabolism. These IDHs exhibit distinct substrate preferences for different inositol isomers, and the study provides insights into substrate specificity through modeling and sequence alignments.
MICROBIOLOGY SPECTRUM
(2022)
Review
Oncology
Leenu Reinsalu, Marju Puurand, Vladimir Chekulayev, Sten Miller, Igor Shevchuk, Kersti Tepp, Egle Rebane-Klemm, Natalja Timohhina, Anton Terasmaa, Tuuli Kaambre
Summary: Metabolic plasticity is the ability of cells to adjust metabolism to environmental changes. Cancer cells exhibit increased metabolic plasticity, allowing them to have a survival advantage and higher proliferative capacity. This enhanced plasticity is characterized by changes in adenine nucleotide transport, impaired regulation of VDAC and reprogrammed energy transfer circuits like AK and CK pathways.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Xiang Xu, Guangjin Ding, Caizhi Liu, Yuhan Ding, Xiaoxin Chen, Xiaoli Huang, Chen-Song Zhang, Shanxin Lu, Yunpeng Zhang, Yuanyong Huang, Zhaosu Chen, Wei Wei, Lujian Liao, Shu-Hai Lin, Jingya Li, Wei Liu, Jiwen Li, Sheng-Cai Lin, Xinran Ma, Jiemin Wong
Summary: The study reveals that UHRF1 acts as a novel gate-keeper of AMPK, regulating cellular energy metabolism and playing critical roles in glucose and lipid metabolism.