Article
Multidisciplinary Sciences
Francisco J. Sanchez-Rivera, Jeremy Ryan, Yadira M. Soto-Feliciano, Mary Clare Beytagh, Lucius Xuan, David M. Feldser, Michael T. Hemann, Jesse Zamudio, Nadya Dimitrova, Anthony Letai, Tyler Jacks
Summary: The level of mitochondrial apoptotic priming is a critical determinant of cell fate upon p53 reactivation, with cells having high initial priming tending to undergo apoptosis and cells with low priming tending to survive and arrest in the cell cycle. Manipulating the priming levels through BCL-2 or BCL-XL expression or inhibition can affect the outcome of p53 restoration, highlighting mitochondrial apoptotic priming as a key factor in determining cell fate. Moreover, less primed cells can be forced into apoptotic cell fate following p53 activation using p53-independent drugs that increase apoptotic priming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Food Science & Technology
Silu Hou, Yuqiang Cheng, Zhaofei Wang, Luming Xia, Jian Wang, Hengan Wang, Jianhe Sun, Jingjiao Ma, Yaxian Yan
Summary: This study investigated the toxic effects of deoxynivalenol (DON) on gastric mucosal epithelial cells and found that DON can inhibit cell activity, induce DNA damage, apoptosis, and cell cycle arrest. These findings are important for understanding the cytotoxicity and gastric diseases caused by DON.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Engineering, Environmental
Junke Wang, Tianxin Zhao, Jiadong Chen, Lian Kang, Yuexin Ei, Yuhao Wu, Lindong Han, Lianju Shen, Chunlan Long, Shengde Wu, Guanghui Wei
Summary: The research revealed that DEHP disrupts testicular development, lowers serum testosterone levels in prepubertal mice, induces cell apoptosis and cell cycle arrest in TM3 cells. The p53 signaling pathway plays a crucial role in DEHP-induced prepubertal testicular injuries by promoting cell apoptosis and inhibiting cell proliferation.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Zhe Hao, Qian Yuan, Hui Tang, Chuntao Lei, Yu Chen, Hua Su, Chun Zhang
Summary: P53 is a master regulator involved in the progression of acute kidney injury (AKI). The role of Mitotic arrest deficient 2 like 2 (MAD2B) in AKI is unclear. This study demonstrates that MAD2B functions as an endogenous suppressor of p53. MAD2B knockout enhances the upregulation of p53 in cisplatin-induced AKI, leading to renal function deterioration, G1 phase arrest, and apoptosis of tubular epithelial cells. Mechanistically, MAD2B deficiency activates anaphase-promoting complex/cyclosome (APC/C), which inhibits the p53-directed E3 ligase MDM2. Decreased MDM2 results in the upregulation of p53.
Review
Biochemistry & Molecular Biology
Hongbo Men, He Cai, Quanli Cheng, Wenqian Zhou, Xiang Wang, Shan Huang, Yang Zheng, Lu Cai
Summary: The transcription factor p53 plays a critical role in cardiac development and maintenance of normal heart function, but it also promotes the development of cardiovascular diseases. This dual role of p53 makes it a potential target for therapies targeting CVD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Jin-yi Liu, Wei-qi Fu, Xiang-jin Zheng, Wan Li, Li-wen Ren, Jin-hua Wang, Cui Yang, Guan-hua Du
Summary: Avasimibe demonstrated potent anticancer effects on human glioblastoma cells by inhibiting proliferation, inducing apoptosis, and regulating multiple signaling pathways. The drug showed promising potential as a chemotherapy treatment for glioblastoma.
ACTA PHARMACOLOGICA SINICA
(2021)
Review
Oncology
Vinesh Dhokia, John A. Y. Moss, Salvador Macip, Joanna L. Fox
Summary: Cellular senescence and apoptosis were historically considered as distinct cell fate pathways, but they share common proteins. p53 plays a key role in determining cell fate, but its decision-making process is not fully understood. Cell fate is dynamic and can be shifted by the right combination of activators and inhibitors. This review focuses on the regulation and induction of apoptosis and senescence, as well as their alterations in chronic diseases.
Review
Cell Biology
Sydney Treichel, Marie-Dominique Filippi
Summary: Hematopoietic stem cells have the ability to self-renew or differentiate into various blood cell lineages. The cell fate decisions of self-renewal or differentiation must be tightly controlled to prevent diseases like bone marrow failure or leukemia. Studies have shown that the cell cycle length plays a crucial role in hematopoietic stem cell fate. Cell cycle kinetics, divisional history, asymmetric cell divisions, metabolic and organelle activity all have an impact on hematopoietic stem cell fate decisions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Jia Liu, Liangyan Deng, Lingyu Wang, Die Qian, Chengxun He, Qiang Ren, Qing Zhang, Yunhui Chen
Summary: The study suggests that Licochalcone A (LCA) has great therapeutic potential for esophageal cancer (EC) by regulating the p53 signaling pathway to induce cell cycle arrest and apoptosis. In vitro experiments showed that LCA inhibited EC cell proliferation, migration, and invasion, and promoted apoptosis. In vivo experiments demonstrated that LCA administration inhibited tumor growth without causing significant toxicities.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Wenshuang Wu, Tao Wei, ZhiHui Li, Jingqiang Zhu
Summary: rAd-p53 sensitizes PTC cells to PTX by increasing p53 levels, leading to S arrest, G2/M arrest, and apoptosis. The combination of rAd-p53 + PTX inhibits tumor growth and induces apoptosis through p53-dependent mechanisms.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jonathan M. Pojer, Samuel A. Manning, Benjamin Kroeger, Shu Kondo, Kieran F. Harvey
Summary: The Hippo pathway plays a critical role in regulating organ growth and cell fate, specifically in the context of R8 photoreceptor cells. The study reveals important differences in the expression and localization of key proteins in the Hippo pathway between R8 cells and growing epithelial organs, shedding light on the complex signaling network involved in organ growth and cell fate decision.
Article
Pharmacology & Pharmacy
Mir Mohd Faheem, Madhulika Bhagat, Pooja Sharma, Rythem Anand
Summary: The study describes the preparation, characterization, and anti-cancer evaluation of silver nanoparticles synthesized using an aqueous extract of Bergenia ligulata as a reducing agent. The silver nanoparticles showed strong cytotoxic effects on human breast cancer cells and induced apoptosis through mitochondrial damage and oxidative stress. Moreover, the nanoparticles had little or no cytotoxic effect on p53-deficient cancer cells. These findings suggest that Bergenia ligulata silver nanoparticles have promising anti-cancer potential and could be a cost-effective and environmentally friendly treatment strategy.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Miao Zhang, Xiaowen Bi, Shuai Liu, Yu Liu, Qiyu Wang
Summary: This study reveals for the first time that OBS triggers senescence in pituitary cells via the p53-p21-RB signaling pathway. OBS inhibits cell proliferation, induces cell cycle arrest at the G1 phase, and downregulates the expression of key proteins involved in the G1/S transition. This study provides new perspectives for understanding the potential toxicity of OBS.
Article
Oncology
Haini Wang, Junli Zuo
Summary: Overexpressed survivin is associated with worse survival of several types of human tumors. In this study, the antitumor activity of shikonin in non-small-cell lung cancer (NSCLC) by regulating survivin pathway was investigated. Result showed that shikonin inhibited the NSCLC H1299 cell proliferation in a dose-dependent manner. Moreover, shikonin fits well with survivin by molecular docking. Shikonin also inhibited the mRNA expression and protein level of survivin in H1299 cells. Shikonin arrested H1299 cell cycle at the G0/G1 phase by regulating CDK/cyclin family members. In addition, shikonin regulated the expression of X-linked inhibitor of apoptosis- (XIAP-) mediated caspases 3 and 9, thus leading to the damage of mitochondrial membrane potential and induction of H1299 cell apoptosis. Overall, shikonin inhibited H1299 cell growth by inducing apoptosis and blocking the cell cycle. The underlying mechanism involves targeting survivin, which subsequently regulates the protein expression of XIAP/caspase 3/9, CDK2/4, and cyclin E/D1. Thus, shikonin, a survivin inhibitor, is a promising therapeutic strategy in NSCLC treatment.
ANALYTICAL CELLULAR PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Guilherme Freimann Wermelinger, Lucas Rubini, Anna Carolina Carvalho da Fonseca, Gabriel Ouverney, Rafael P. R. F. de Oliveira, Acacio S. de Souza, Luana S. M. Forezi, Gabriel Limaverde-Sousa, Sergio Pinheiro, Bruno Kaufmann Robbs
Summary: Oral squamous cell carcinoma (OSCC) is the majority of oral cancers and the eighth most common cancer in men. Current chemotherapeutics have significant side effects, necessitating the development of new anti-cancer agents. In this study, new 1,2,3-triazole-chalcone hybrids were synthesized and evaluated against OSCC, showing great cytotoxicity and selectivity. The compound 1f was found to induce apoptosis and cell cycle arrest, and it also showed potential affinity for the MDM2 protein. Overall, 1f is a promising lead for a new chemotherapeutic drug against OSCC and possibly other types of cancers.
Article
Multidisciplinary Sciences
Rajni Kumari, Ruhi S. Deshmukh, Sanjeev Das
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Nathan J. Schauer, Xiaoxi Liu, Robert S. Magin, Laura M. Doherty, Wai Cheung Chan, Scott B. Ficarro, Wanyi Hu, Rebekka M. Roberts, Roxana E. Iacob, Bjoern Stolte, Andrew O. Giacomelli, Sumner Perera, Kyle McKay, Sarah A. Boswell, Ellen L. Weisberg, Arghya Ray, Dharminder Chauhan, Sirano Dhe-Paganon, Ken C. Anderson, James D. Griffin, Jianing Li, William C. Hahn, Peter K. Sorger, John R. Engen, Kimberly Stegmaier, Jarrod A. Marto, Sara J. Buhrlage
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Jason Qian, Zhi-xiang Lu, Christopher P. Mancuso, Han-Ying Jhuang, Rocio del Carmen Barajas-Ornelas, Sarah A. Boswell, Fernando H. Ramirez-Guadiana, Victoria Jones, Akhila Sonti, Kole Sedlack, Lior Artzi, Giyoung Jung, Mohammad Arammash, Mary E. Pettit, Michael Melfi, Lorena Lyon, Sian V. Owen, Michael Baym, Ahmad S. Khalil, Pamela A. Silver, David Z. Rudner, Michael Springer
Article
Multidisciplinary Sciences
Jason Qian, Sarah A. Boswell, Christopher Chidley, Zhi-xiang Lu, Mary E. Pettit, Benjamin L. Gaudio, Jesse M. Fajnzylber, Ryan T. Ingram, Rebecca H. Ward, Jonathan Z. Li, Michael Springer
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Steve Rodriguez, Clemens Hug, Petar Todorov, Nienke Moret, Sarah A. Boswell, Kyle Evans, George Zhou, Nathan T. Johnson, Bradley T. Hyman, Peter K. Sorger, Mark W. Albers, Artem Sokolov
Summary: The machine learning framework DRIAD quantifies potential associations between the severity of Alzheimer's Disease pathology and gene-based molecular mechanisms, facilitating drug repurposing and potentially identifying drugs suitable for clinical trials.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Analytical
Christopher P. Mancuso, Zhi-Xiang Lu, Jason Qian, Sarah A. Boswell, Michael Springer
Summary: Quantitative diagnostics are crucial for controlling infectious diseases and informing treatment strategies. The qRPA technology provides semiquantitative information and may be useful for monitoring the progress of viral infections or other diseases.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Priyanka Priyanka, Madhur Sharma, Sanjeev Das, Sandeep Saxena
Summary: In this study, an upregulated lncRNA, HMS, was identified in lung adenocarcinoma patient database, which has a significant impact on cell proliferation and colony formation of cancer cells. It was found that HMS stabilizes HOXC10 mRNA to sustain the invasive phenotype of cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Alka Gupta, Amandeep Vats, Anindita Ghosal, Kamal Mandal, Rajesh Sarkar, Indrashis Bhattacharya, Sanjeev Das, Rahul Pal, Subeer S. Majumdar
Summary: Sertoli cells are the sole target of follicle-stimulating hormone (FSH) in the testis and their maturation during puberty is regulated by miR-92a-3p. The decline of miR-92a-3p during puberty is accompanied by elevated expressions of FSH Receptor, Claudin11, and Klf4 in Sertoli cells. Overexpression of miR-92a-3p in post-pubertal testes leads to compromised Sertoli cell function and infertility.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Priyanka Priyanka, Madhur Sharma, Sanjeev Das, Sandeep Saxena
Summary: E2F1 induces the expression of lncRNA EMSLR in lung adenocarcinoma and lung squamous cell carcinoma, and it is involved in regulating cell proliferation and differentiation signaling pathways. EMSLR functions by repressing the promoter activity of LncPRESS1, and C-MYC plays a role in the regulation network of EMSLR and LncPRESS1.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Laura M. Doherty, Caitlin E. Mills, Sarah A. Boswell, Xiaoxi Liu, Charles Tapley Hoyt, Benjamin Gyori, Sara J. Buhrlage, Peter K. Sorger, Silke Hauf
Summary: This study establishes a knowledgebase of DUB activities, co-dependent genes, and substrates, utilizing targeted experiments and systematic mining of functional genomic databases. The findings provide insights into the important role of DUBs in regulating cellular activities and suggest their potential as therapeutic targets for cancer and other diseases.
Article
Oncology
Shalakha Sharma, Witty Tyagi, Rohini Tamang, Sanjeev Das
Summary: This study reveals that HDAC5 interacts with and deacetylates SATB1, with the acetylation of SATB1 at lysine 411 regulated by TIP60 acetyltransferase. HDAC5-mediated deacetylation is critical for the downregulation of key tumor suppressor genes by SATB1 and the repression of SDHA-induced epigenetic remodeling and anti-proliferative transcriptional program. These findings shed light on the molecular mechanisms underlying SATB1-promoted tumor growth and metastasis.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Anjali Barnwal, Rohini Tamang, Jayanta Bhattacharyya
Summary: The study found that Ponatinib can inhibit the induced PD-L1 levels by regulating HIF-1a expression, thus altering the tumor microenvironment. This research provides a new therapeutic insight of Ponatinib for the treatment of solid tumors, either alone or in combination with other drugs that induce PD-L1 expression.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Madhurima Ghosh, Sanjeev Das
Summary: PRAMEF2 is repressed under conditions of altered metabolic homeostasis in a FOXP3-dependent manner, and mediates polyubiquitylation of LATS1 kinase of the Hippo/YAP pathway, leading to enhanced nuclear accumulation of YAP and increased expression of proliferative and metastatic genes. This promotes a malignant phenotype.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Anita K. Mehta, Emily M. Cheney, Christina A. Hartl, Constantia Pantelidou, Madisson Oliwa, Jessica A. Castrillon, Jia-Ren Lin, Katie E. Hurst, Mateus de Oliveira Taveira, Nathan T. Johnson, William M. Oldham, Marian Kalocsay, Matthew J. Berberich, Sarah A. Boswell, Aditi Kothari, Shawn Johnson, Deborah A. Dillon, Mikel Lipschitz, Scott Rodig, Sandro Santagata, Judy E. Garber, Nadine Tung, Jose Yelamos, Jessica E. Thaxton, Elizabeth A. Mittendorf, Peter K. Sorger, Geoffrey I. Shapiro, Jennifer L. Guerriero
Summary: The study reveals that PARP inhibition affects macrophage metabolism and function in BRCA-associated TNBC, and combining PARP inhibition with CSF1R blockade therapy enhances antitumor immunity and prolongs survival. Targeting macrophage-mediated immune suppression can improve the efficacy of PARP inhibitors.
Article
Biochemistry & Molecular Biology
Marc Hafner, Caitlin E. Mills, Kartik Subramanian, Chen Chen, Mirra Chung, Sarah A. Boswell, Robert A. Everley, Changchang Liu, Charlotte S. Walmsley, Dejan Juric, Peter K. Sorger
CELL CHEMICAL BIOLOGY
(2019)