Article
Biochemistry & Molecular Biology
Yumi Ueki, Michael A. Hadders, Melanie B. Weisser, Isha Nasa, Paula Sotelo-Parrilla, Lauren E. Cressey, Tanmay Gupta, Emil P. T. Hertz, Thomas Kruse, Guillermo Montoya, A. Arockia Jeyaprakash, Arminja Kettenbach, Susanne M. A. Lens, Jakob Nilsson
Summary: The study reveals the structure and function of the PP2A-B56-hSgo1 complex during mitosis, highlighting the essential role of a conserved pocket on the B56 regulatory subunit for hSgo1 binding and cohesion protection. Additionally, it shows that hSgo1 inhibits the binding of PP2A-B56 substrates and that PP2A-B56 dephosphorylates Cdk1 sites on hSgo1 to regulate cohesin interactions. Overall, the research provides important insights into cohesion protection during mitosis.
Review
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Oscar Fernandez-Capetillo, Emilio Lecona
Summary: Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in ensuring the faithful duplication of genetic information. Ubiquitination and SUMOylation not only serve as signals for the extraction of factors from chromatin, but also mediate the disassembly of the replisome and preserve genomic stability in DNA replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Agnieszka T. Kawashima, Cassandra Wong, Gema Lorden, Charles C. King, Pablo Lara-Gonzalez, Arshad Desai, Anne-Claude Gingras, Alexandra C. Newton
Summary: PHLPP1 is a tumor suppressor protein that is dynamically regulated in a cell cycle-dependent manner, with its N-terminal extension (NTE) being hyperphosphorylated by Cdk1 during mitosis. This phosphorylation regulates its binding to mitotic proteins, such as KNL1 and TPX2, potentially playing a role in its tumor-suppressive function.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Cell Biology
Arzu Ulu, Wonkyung Oh, Yan Zuo, Jeffrey A. Frost
Summary: Net1, an overexpressed gene in various cancers, plays a crucial role in cancer cell motility and proliferation, as well as mitotic progression. The mitotic kinase Cdk1 phosphorylates Net1 at multiple sites, negatively regulating its ability to signal to RhoA and alter actin cytoskeletal organization. The study also showed that inhibition of Cdk1 increased Net1 activity and affected its localization to the plasma membrane and cortical F-actin accumulation.
CELLULAR SIGNALLING
(2021)
Review
Cell Biology
Benjamin Lacroix, Thierry Lorca, Anna Castro
Summary: Proper repartition of DNA during cell division requires major physical changes, including nuclear envelope breakdown, DNA condensation, and spindle formation. These changes are regulated by the balance between protein kinases and phosphatases. While the role of kinases in mitosis has been extensively studied, the importance of phosphatases has been underestimated. Recent research has highlighted the crucial role of the phosphatase holoenzyme PP2A-B55 in regulating cell division events. This review focuses on the latest insights into the structure, biochemistry, and enzymatic mechanisms of PP2A-B55 phosphatase and its regulators.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Yi Xiao, Yuanhong Chen, Jianan Chen, Jixin Dong
Summary: This study investigates the role of ASPP2 in pancreatic cancer and its phosphorylation regulation during mitosis. The findings reveal that ASPP2 is phosphorylated by CDK1 during mitosis and its depletion attenuates pancreatic cancer cell growth. Additionally, ASPP2 significantly affects the transcriptome landscape of YAP-related genes.
Article
Cell Biology
Lisa Donker, Ronja Houtekamer, Marjolein Vliem, Francois Sipieter, Helena Canever, Manuel Gomez-Gonzalez, Miquel Bosch-Padros, Willem-Jan Pannekoek, Xavier Trepat, Nicolas Borghi, Martijn Gloerich
Summary: Epithelial cells adapt their rate of cell division by sensing changes in cell number through mechanosensitive E-cadherin adhesions, which control G2/M cell-cycle progression.
Article
Biochemistry & Molecular Biology
Virginie Emond-Fraser, Myreille Larouche, Peter Kubiniok, Eric Bonneil, Jingjing Li, Mohammed Bourouh, Laura Frizzi, Pierre Thibault, Vincent Archambault
Summary: Mitotic exit necessitates dephosphorylation of proteins previously phosphorylated during mitosis. PP2A-B55 regulates the dephosphorylation of emerin in Drosophila, which in turn determines the timing of nuclear envelope reformation. This regulation is essential for embryonic development and may be conserved across species.
Article
Cell Biology
Lei Wang, Thomas Kruse, Blanca Lopez-Mendez, Yuqing Zhang, Chunlin Song, Lei Zhu, Bing Li, Jing Fang, Zhimin Lu, Jakob Nilsson, Gang Zhang
Summary: The Bub1 and BubR1 kinetochore proteins are involved in chromosome segregation and the mitotic checkpoint. While Bub1 is a kinase, BubR1 localizes a phosphatase to kinetochores in humans. This study shows that integrating kinase and phosphatase activities within the Bub complex is necessary for maintaining proper mitotic progression.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Cell Biology
Katarzyna Majstrowicz, Ulrike Honnert, Petra Nikolaus, Vera Schwarz, Stefanie J. Oeding, Sandra A. Hemkemeyer, Martin Baehler
Summary: Myo19 plays a crucial role in regulating mitochondrial functions, cell division, and cell-matrix adhesion. It affects focal adhesions and mitochondrial structure, with these effects primarily attributed to the interference of Miro on the coordination between Myo19 and microtubule-based motor activities.
JOURNAL OF CELL SCIENCE
(2021)
Article
Developmental Biology
Jiahui Du, Junjun Jing, Shuo Chen, Yuan Yuan, Jifan Feng, Thach-Vu Ho, Prerna Sehgal, Jian Xu, Xinquan Jiang, Yang Chai
Summary: The research reveals that Arid1a maintains tissue homeostasis by inhibiting the Aurka-Cdk1 axis, limiting proliferation of TACs, and promoting their differentiation, while loss of Arid1a leads to reduction of the MSC population.
Article
Cell Biology
Aymen al-Rawi, Edward Kaye, Svitlana Korolchuk, Jane A. Endicott, Tony Ly
Summary: Ordered protein phosphorylation by CDKs is a key mechanism for regulating the cell cycle. We show how CDK1 activity and non-catalytic CDK1 subunits contribute to the choice of substrate and site of phosphorylation using a fixed cell kinase assay and phosphoproteomics. Contrary to the model of CDK1 as an exclusively proline-directed kinase, Cyclin A and Cks1 enhance non-proline-directed phosphorylation, preferably on sites with a +3 lysine residue.
Article
Cell Biology
Chenxi Zhou, Hayden A. Homer
Summary: During fertilization in mice, Cdk1 activity, cell division, and pronuclear formation go through two pauses, with the first pause triggering cell division and the second pause triggering pronuclear formation. Both pauses require the inhibitory Cdk1 kinase Wee1B, but only the first pause involves the degradation of cyclin B1.
Article
Biochemistry & Molecular Biology
Enshuang Guo, Jiankun Yang, Lei Li, Jia Chen, Hongqiang Liu
Summary: The drug resistance of single-target therapy has become a challenging clinical problem. Combination therapy, specifically targeting TACC3 and CDK1, may be a promising approach to overcome or delay drug resistance in hepatocellular carcinoma (HCC).
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wen-Hsuan Chang, Yinzhe Liu, Emma A. Hammes, Kirsten L. Bryant, Richard A. Cerione, Marc A. Antonyak
Summary: In this study, it was discovered that the inhibitor of apoptosis protein Survivin mediates the cooperative actions of KRAS and MYC in pancreatic cancer. Survivin expression is regulated by KRAS through the extracellular signal-regulated kinase 1/2 pathway, which protects MYC from degradation and enhances its transcriptional activity. Targeting Survivin can effectively downregulate MYC expression and inhibit the growth of pancreatic cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shang-Wei Lin, Kuan-Hsuan Su, Yi-Qi Yeh, U-Ser Jeng, Chun-Ming Wu, Hsiao-Ching Yang
Summary: This article introduces a strategy for determining protein hydration structures using small-angle X-ray and neutron scattering in combination with molecular dynamics simulation, to describe the hydrodynamics conformation transitions of biomacromolecules.
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Shao-An Wang, Ming-Jer Young, Yi-Chang Wang, Shu-Hui Chen, Chia-Yu Liu, Yao-An Lo, Hung-Hsiang Jen, Kai-Cheng Hsu, Jan-Jong Hung
Summary: USP24 plays a crucial role in repressing DNA-damage repair activity and increasing ABC transporters levels, leading to drug resistance. The novel USP24 inhibitor NCI677397 shows potential in suppressing drug resistance by targeting these mechanisms.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Chemistry, Physical
Kuan-Hsuan Su, Chin-Teng Wu, Shang-Wei Lin, Seiji Mori, Wei-Min Liu, Hsiao-Ching Yang
Summary: This study focuses on the dynamics of enzymes and the mechanism of substrate binding and leaving, investigating the relationship between protein interior tunnel structures and dynamics through molecular dynamics simulations and adaptive basing force umbrella sampling simulations. The theoretical analysis provides insights into the decisive role of the substrate tunnel binding process of the enzyme mechanism, potentially useful in drug design and protein engineering contexts.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Oncology
An-Chih Wu, Wen-Bin Yang, Kwang-Yu Chang, Jung-Shun Lee, Jing-Ping Liou, Ruei-Yuan Su, Siao Muk Cheng, Daw-Yang Hwang, Ushio Kikkawa, Tsung- Hsu, Chih-Yang Wang, Wen-Chang Chang, Pin-Yuan Chen, Jian-Ying Chuang
Summary: This study identifies LINC00461 as a significantly increased lncRNA in stem-like/treatment-resistant GBM cells, and demonstrates that targeting the HDAC6/RBP axis through LINC00461 can suppress GBM cell proliferation and prolong patient survival.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Wen-Bin Yang, An-Chih Wu, Tsung- Hsu, Jing-Ping Liou, Wei-Lun Lo, Kwang-Yu Chang, Pin-Yuan Chen, Ushio Kikkawa, Shung-Tai Yang, Tzu-Jen Kao, Ruei-Ming Chen, Wen-Chang Chang, Chiung-Yuan Ko, Jian-Ying Chuang
Summary: This study illustrates the relationship between DDR gene expression and treatment resistance in GBM, highlighting the potential therapeutic role of the HDAC6 inhibitor MPT0B291 in GBM cells. MPT0B291 effectively reduces the expression of DNA damage repair genes, enhances cytotoxicity in GBM cells, and extends survival in mouse models.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yin-Hsun Feng, Sher-Wei Lim, Hong-Yi Lin, Shao-An Wang, Sung-Po Hsu, Tzu-Jen Kao, Chiung-Yuan Ko, Tsung- Hsu
Summary: Allopregnanolone (allo) has the potential to be a treatment for glioblastoma (GBM). It enhances the inhibitory effect of temozolomide (TMZ) on cell survival and proliferation, inhibits cell migration, and induces apoptosis. Allo also decreases the expression of DPYSL3/S100A11 and induces DNA damage to suppress GBM cell survival.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Kuan Zhang, Erica Yao, Shao-An Wang, Ethan Chuang, Julia Wong, Liliana Minichiello, Andrew Schroeder, Walter Eckalbar, Paul J. Wolters, Pao-Tien Chuang
Summary: The autonomic nerve and alveolar myofibroblast form a functional unit in mice, where myofibroblasts secrete neurotrophins to promote neurite extension/survival and neurotransmitters released from autonomic terminals are necessary for myofibroblast proliferation and migration. Planar cell polarity signaling regulates the cytoskeleton and neurotransmitter trafficking/release from autonomic nerves.
DEVELOPMENTAL CELL
(2022)
Article
Oncology
Chia-Hung Chien, Wen-Bin Yang, Jian-Ying Chuang, Jung-Shun Lee, Wei-An Liao, Chih-Yuan Huang, Pin-Yuan Chen, An-Chih Wu, Shun-Tai Yang, Chien-Cheng Lai, Pei- Chi, Jui-Mei Chu, Siao Muk Cheng, Chan-Chuan Liu, Daw-Yang Hwang, Shang-Hung Chen, Kwang-Yu Chang
Summary: This study demonstrates that SH3GLB1 promotes resistance to temozolomide through autophagy-mediated alteration of mitochondrial function in glioblastoma.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ming-Zhen Chen, Shao-An Wang, Shih-Chang Hsu, Kleiton Augusto Santos Silva, Feng-Ming Yang
Summary: House dust mite extract stimulates the TLR2/4 signaling pathway involving the sNASP/TRAF6 axis, leading to mucus overproduction and airway inflammation. The PEP-NASP peptide shows potential as a target for asthma treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hong-Yi Lin, Sher-Wei Lim, Tsung- Hsu, Wen-Bin Yang, Chi-Chen Huang, Yu-Ting Tsai, Wen-Chang Chang, Chiung-Yuan Ko
Summary: Cancer cells have increased and persistent oxidative stress due to reactive oxygen species (ROS) and stimulate the antioxidant system. However, overexpressed antioxidant enzymes can lead to drug resistance. In glioblastoma (GBM) cells, loss of the transcription factor CEBPD inhibits cell viability and accelerates intracellular accumulation of hydrogen peroxide (H2O2).
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Review
Biochemistry & Molecular Biology
Tzu-Jen Kao, Chien-Liang Lin, Wen-Bin Yang, Hao-Yi Li, Tsung- Hsu
Summary: In this review, the researchers summarize current knowledge on lipid metabolism in GBM, specifically focusing on the development of TMZ resistance. Dysregulated lipid metabolism has been identified as a contributing factor to TMZ resistance in GBM, and targeting lipid metabolism may offer a promising approach for overcoming resistance and improving outcomes. The review highlights key metabolites and proteins involved in lipid synthesis, uptake, and utilization, as well as recent advances in metabolomics to study lipid metabolism in GBM.
LIPIDS IN HEALTH AND DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Kai-Hsin Chang, Yu-Chiang Peng, Kuan-Hsuan Su, Yi-Hsien Lin, Jiun-Chi Liu, Ying-Hsuan Liu, Chao-Hsien Hsu, Hsiao-Ching Yang, Pi-Tai Chou
Summary: Solvent-catalyzed proton transfer via the relay of hydrogen bonds was studied using a new class of 1H-pyrrolo[3,2-g]quinolines and their derivatives. The fluorescence dynamics showed a relationship between precursor and successor molecules and an increasing overall excited-state proton transfer rate with increasing basicity. Molecular dynamics simulation revealed cyclic H-bonded PyrQs incorporating methanol molecules, and different proton tunneling rates were observed for PyrQ and PyrQ-D.
Article
Cell Biology
Yu-Ting Tsai, Wei-Lun Lo, Pin-Yuan Chen, Chiung-Yuan Ko, Jian-Ying Chuang, Tzu-Jen Kao, Wen-Bing Yang, Kwang-Yu Chang, Chia-Yang Hung, Ushio Kikkawa, Wen-Chang Chang, Tsung- Hsu
Summary: Sp1-regulated PGE2 production activates FAO and TCA cycle in mitochondria, resulting in TMZ resistance in GBM. These findings provide a new strategy to attenuate drug resistance or to re-sensitize recurrent GBM.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Cell Biology
Ming-Jer Young, Yung-Ching Chen, Shao-An Wang, Hui-Ping Chang, Wen-Bin Yang, Chia-Chi Lee, Chia-Yu Liu, Yau-Lin Tseng, Yi-Ching Wang, H. Sunny Sun, Wen-Chang Chang, Jan-Jong Hung
Summary: Decreased Sp1 levels in lung cancer are associated with poor prognosis and are related to estrogen. It has been found that E2 can decrease Sp1 levels by increasing the expression of RNF4, and ultimately lead to malignancy in lung cancer.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)