Article
Cell Biology
Gembu Maryu, Qiong Yang
Summary: The nucleocytoplasmic compartmentalization significantly modulates the spatiotemporal dynamics of Cdk1, which is important for the oscillation robustness of the cell cycle. Nucleus-absent cells display highly tunable frequency while nucleus-present cells maintain constant frequency against variations in cyclin B1. The biphasic activation of Cdk1 and the spatial compartmentalization may coordinate the accurate ordering of different downstream events.
Review
Oncology
Qiushi Wang, Ann M. Bode, Tianshun Zhang
Summary: Cyclin dependent kinases (CDKs) are proposed as promising candidate targets for cancer treatment, as they play a critical role in cell cycle progression and have higher expression in cancer tissues. CDK1 activation is closely associated with tumorigenesis and its associated proteins participate in multiple oncogenic pathways. Small molecules targeting CDK1 or multiple CDKs have been developed and evaluated in preclinical studies, including some human clinical trials.
NPJ PRECISION ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixo Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia Guarguaglini, Sabrina Di Bartolomeo, Francesco Cecconi
Summary: AMBRA1 is a key factor for nervous system development, primarily associated with autophagy and cell proliferation control. This study reveals that AMBRA1 is phosphorylated during mitosis and is critical for spindle function and orientation, driven by NUMA1 protein. The localization and dynamics of NUMA1 are dependent on AMBRA1 presence, phosphorylation, and binding ability. These findings suggest an additional role of AMBRA1 in tissue morphogenesis and differentiation, which could have implications for development and cancer oncogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
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
Biochemistry & Molecular Biology
Lau Yan Ng, Hoi Tang Ma, Randy Y. C. Poon
Summary: In this study, an inverse relationship between cyclin A and CDC25A, two CDK activators, was uncovered. Destruction of cyclin A promoted an acute accumulation of CDC25A, mainly through transcriptional upregulation rather than protein stability changes. This compensatory mechanism involving CDC25A ensures timely mitotic entry at different levels of cyclin A deficiency.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jonathan B. Asfaha, Mihkel Ord, Christopher R. Carlson, Ilona Faustova, Mart Loog, David O. Morgan
Summary: Cell-cycle progression is driven by the phosphorylation of cyclin-dependent kinase (Cdk) substrates. The order of substrate phosphorylation depends on the rise in Cdk activity during the cell cycle and variations in substrate docking. Ndd1, a transcriptional co-activator, is phosphorylated by Cdk1 to promote mitotic cyclin gene transcription, but high Cdk1 activity leads to inhibition of gene expression and degradation of Ndd1 through multisite phosphorylation.
Article
Biochemistry & Molecular Biology
Jiayi Chen, Mei Li, Yeqing Liu, Tangming Guan, Xiao Yang, Yalei Wen, Yingjie Zhu, Zeyu Xiao, Xiangchun Shen, Haoxing Zhang, Hui Tang, Tongzheng Liu
Summary: CDK1 and PIN1 have been identified as previously uncharacterized regulators of pVHL in human cancers harboring wild-type VHL. They cooperate to modulate the protein turnover of pVHL, promoting tumor growth, chemotherapeutic resistance, and metastasis. Targeting CDK1/PIN1 is a potential strategy for the treatment of multiple cancers with wild-type VHL.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Cell Biology
Richard Odle, Oliver Florey, Nicholas T. Ktistakis, Simon J. Cook
Summary: Autophagy and cap-dependent mRNA translation are tightly regulated during mitosis, with a switch from mTORC1 to CDK1-mediated regulation being a significant factor. Recent studies have shown repression of autophagy initiation and maintenance of cap-dependent mRNA translation even when mTORC1 activity is repressed. This highlights the complexity of regulation during mitosis and the need for further research in this area.
TRENDS IN CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Yu-gang Huang, Dan Li, Li Wang, Xiao-min Su, Xian-bin Tang
Summary: The study revealed that CENPF is significantly overexpressed in ACC patients, which is positively correlated with tumor stage and associated with unfavorable overall survival in ACC patients. GSEA analysis suggested that CENPF is mainly involved in regulating the G2/M phase of the cell cycle and the p53 signaling pathway. Experimental findings indicated that the interaction between CENPF and CDK1 facilitates the G2/M phase transition, cell proliferation, and potentially induces a p53-mediated anti-tumor effect in ACC. Additionally, immune infiltration analysis highlighted the potential use of CENPF inhibitors like Cisplatin, Sunitinib, and Etoposide for ACC therapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Yipeng Feng, Te Zhang, Zeyu Zhang, Yingkuang Liang, Hui Wang, Yuzhong Chen, Xinnian Yu, Xuming Song, Qixing Mao, Wenjie Xia, Bing Chen, Lin Xu, Gaochao Dong, Feng Jiang
Summary: This study identified a super-enhancer-driven lncRNA, LINC00880, which plays a significant regulatory role in lung adenocarcinoma. LINC00880 interacts with proteins CDK1 and PRDX1 to form a complex, thereby promoting the activation of the PI3K/AKT pathway and contributing to the development and progression of lung adenocarcinoma.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Ho Wai Lau, Hoi Tang Ma, Tsz Kwan Yeung, Man Yee Tam, Danyi Zheng, Siu Ki Chu, Randy Yat Choi Poon
Summary: One of the most intriguing features of cell-cycle control is the quantitative difference between G(2)-M and G(1)-S CDKs in human cells, where CDK1 and CDK2 play distinct roles in the process of mitosis, with a lower concentration of CDK2 leading to defective anaphase.
Article
Pharmacology & Pharmacy
Guangya Xu, Xueling Yan, Zhongjia Hu, Lulu Zheng, Ke Ding, Yamei Zhang, Yi Qing, Tao Liu, Lijia Cheng, Zheng Shi
Summary: Glucocappasalin (GCP) from Descurainia sophia seeds shows potential antitumor activity in HeLa cervical carcinoma cells. GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways, making it a promising agent for cervical cancer eradication.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pim J. Huis in 't Veld, Sabine Wohlgemuth, Carolin Koerner, Franziska Muller, Petra Janning, Andrea Musacchio
Summary: During cell division into mitosis, CDK1 and Cyclin-B complex phosphorylate proteins, altering their conformations and functions; to study the mitotic protein machinery, a pure and active kinase complex must be reconstituted in vitro; high activity of CDK1:Cyclin-B complex can be achieved through the activation of a Threonine residue in the CDK1 activation loop.
Article
Cell Biology
Yining Hao, Yu Zhu, Fukang Sun, Danfeng Xu, Chenghe Wang
Summary: miR-30c-5p is significantly downregulated in bladder cancer (BCa) and is associated with unfavorable TNM stages and poor prognosis. It exerts its function in BCa by suppressing its target gene PRC1. Thus, miR-30c-5p has the potential to be a valuable biomarker for predicting clinical outcomes in BCa patients.
CELLULAR SIGNALLING
(2023)
Article
Oncology
Tzeh K. Foo, Gabriele Vincelli, Eric Huselid, Joonyoung Her, Haiyan Zheng, Srilatha Simhadri, Meiling Wang, Yanying Huo, Tao Li, Xiaochun Yu, Hong Li, Weixing Zhao, Samuel F. Bunting, Bing Xia
Summary: This study identifies a critical BRCA1 phosphorylation event mediated by ATR and ATM at the T1394 site, which ensures accurate repair of DNA double-strand breaks and maintains chromosomal integrity in the DNA damage response. Additionally, it reveals the impact of multiple BRCA1 variants of unknown significance on T1394 phosphorylation.
Article
Biophysics
Catherine E. Scull, Aaron L. Lucius, David A. Schneider
Summary: This study investigates the structural and functional differences among the three RNA polymerases in eukaryotes, as well as the specific functions and gene expression regulatory mechanisms of the A12 subunit of Pol I.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Ruth Q. Jacobs, Abigail K. Huffines, Marikki Laiho, David A. Schneider
Summary: This study elucidates the mechanism of Pol I inhibition by BMH-21 and represents a critical step forward in the development of this compound and its derivatives for clinical use.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Correction
Biochemistry & Molecular Biology
Lei Shi, Xiangyu Shen, Hengbin Wang, Yuan Shen
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Biology
Adrienne Samani, Rylie M. Hightower, Andrea L. Reid, Katherine G. English, Michael A. Lopez, J. Scott Doyle, Michael J. Conklin, David A. Schneider, Marcas M. Bamman, Jeffrey J. Widrick, David K. Crossman, Min Xie, David Jee, Eric C. Lai, Matthew S. Alexander
Summary: miR-486 plays a significant role in muscle function, with reduced expression associated with Duchenne muscular dystrophy. It is essential for normal muscle function and contributes to pathological remodeling in dystrophin-deficient muscle. Additionally, it serves as a useful biomarker for disease progression. The use of multiple omic platforms is effective in identifying in vivo miR-486 target transcripts.
LIFE SCIENCE ALLIANCE
(2022)
Article
Multidisciplinary Sciences
Xianchun Lan, Song Ding, Tianzhe Zhang, Ying Yi, Conghui Li, Wenwen Jin, Jian Chen, Kaiwei Liang, Hengbin Wang, Wei Jiang
Summary: This study reveals that PCGF6 plays a crucial role in determining the lineage specification of human pluripotent stem cells by promoting neuroectoderm differentiation and repressing mesendoderm differentiation. The activation of the SOX2 gene and the repression of the WNT/beta-catenin signaling pathway are key mechanisms involved in this process.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Linlin Li, Aidong Zhou, Yanjun Wei, Feng Liu, Peng Li, Runping Fang, Li Ma, Sicong Zhang, Longqiang Wang, Jinze Liu, Hope T. Richard, Yiwen Chen, Hengbin Wang, Suyun Huang
Summary: In this study, a previously unidentified oncogenic lncRNA called lncEPAT was discovered to mediate the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT interacts with deubiquitinase USP16 and inhibits its recruitment to chromatin, thereby blocking USP16-mediated H2A deubiquitination and repressing target gene expression. Depletion of lncEPAT promotes USP16-induced cell cycle arrest and cellular senescence, and represses tumor formation in GBM cells.
Article
Biochemistry & Molecular Biology
Zachariah I. Carter, Ruth Q. Jacobs, David A. Schneider, Aaron L. Lucius
Summary: Eukaryotic RNA polymerase II (Pol II) is a crucial enzyme in eukaryotic biology. By using transient-state kinetic techniques, we investigated the single nucleotide addition process of Pol II on a millisecond time scale, aiming to understand its nucleotide incorporation mechanism.
Article
Biochemistry & Molecular Biology
Stephanie Pitts, Hester Liu, Adel Ibrahim, Amit Garg, Catarina Mendes Felgueira, Asma Begum, Wenjun Fan, Selina Teh, Jin-Yih Low, Brittany Ford, David A. Schneider, Ronald Hay, Marikki Laiho
Summary: The study reveals that F-box protein FBXL14 regulates the stability of the Pol I complex and promotes the degradation of specific subunits under transcription stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Abigail K. Huffines, Krysta L. Engel, Sarah L. French, Yinfeng Zhang, Olga V. Viktorovskaya, David A. Schneider
Summary: Transcription of ribosomal DNA by RNA polymerase I (Pol I) is one of the initial steps in ribosome biogenesis. In this study, a mutant form of Pol I, rpa190-F1205H, was used to investigate the link between transcription elongation and ribosome assembly. The mutant Pol I showed increased pause propensity during processive transcription elongation, both in vitro and in vivo. Additionally, alternative pause site preferences were observed in the mutant Pol I in vivo. These findings provide novel insights into Pol I elongation properties and its impact on rRNA processing and ribosome assembly.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Oncology
Ruth Q. Jacobs, Kaila B. Fuller, Stephanie L. Cooper, Zachariah Carter, Marikki Laiho, Aaron L. Lucius, David A. Schneider
Summary: This study evaluates the specificity of the compound BMH-21 on transcription by Pols I, II, and III. The results show that Pol I is more sensitive to inhibition by BMH-21 compared to Pols II and III. These findings support the ongoing development of BMH-21 and its derivatives as potential therapeutic agents.
Article
Multidisciplinary Sciences
Brittany L. Ford, Ting Wei, Hester Liu, Catherine E. Scull, Saman M. Najmi, Stephanie Pitts, Wenjun Fan, David A. Schneider, Marikki Laiho
Summary: This study investigates the role of RPA12 in the regulation of RPA194 in human cancer cells. The results show that RPA12 affects the expression and localization of RPA194 and RPA135, but does not influence the transcription activity of Pol I or its engagement with chromatin. Additionally, RPA12 does not impact the degradation of RPA194 mediated by the small-molecule Pol I inhibitor BMH-21. These findings provide new insights into the regulatory factors controlling the expression of the Pol I catalytic subunit.
Review
Cell Biology
Jiahuan Zheng, Chunxu Chen, Chunqing Guo, Cody Caba, Yufeng Tong, Hengbin Wang
Summary: Ubiquitin-specific peptidase 16 (USP16) is a deubiquitinase involved in gene expression regulation, cell cycle progression, and various other functions. It was identified as a major deubiquitinase for histone H2A and has been found to deubiquitinate other proteins. USP16 is phosphorylated during mitosis and dephosphorylated during the metaphase/anaphase transition. It has been linked to DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility, making it a potential therapeutic target for certain human diseases.
Article
Oncology
Catherine E. Scull, Guy Twa, Yinfeng Zhang, Naiheng J. Yang, Robert N. Hunter III, Corinne E. Augelli-szafran, David A. Schneider
Summary: A newly identified ribosome biogenesis inhibitor, RBI2, has been shown to inhibit multiple types of cancer cells by inducing rapid polyadenylation and degradation of ribosomal RNA. This mechanism of action is distinct from previously described compounds and offers a potential novel pathway for cancer therapeutics targeting ribosome synthesis. This study reveals the importance of ribosome biogenesis in cancer cell growth and highlights the potential of RBI2 as a promising cancer therapeutic.
Article
Cell Biology
Saeid Mohammad Parast, Deli Yu, Chunxu Chen, Amanda J. Dickinson, Chenbei Chang, Hengbin Wang
Summary: In this study, the researchers investigated the role of RSF1 in early embryonic development using Xenopus laevis as a model organism. They found that knockdown of RSF1 resulted in defects in gastrulation as well as neural and neural crest development. Furthermore, they demonstrated that the recognition of the H2AK119ub mark by RSF1 is important for its function during embryonic development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Victoria Sanchez-Martin, David A. Schneider, Matilde Ortiz-Gonzalez, Ana Soriano-Lerma, Angel Linde-Rodriguez, Virginia Perez-Carrasco, Jose Gutierrez-Fernandez, Marta Cuadros, Juan C. Morales, Carlos Gonzalez, Miguel Soriano, Jose A. Garcia-Salcedo
CELL CHEMICAL BIOLOGY
(2021)