Article
Engineering, Biomedical
Suhaila O. Alhaj-Suliman, Youssef W. Naguib, Emad I. Wafa, Sanjib Saha, Kareem Ebeid, Xiangbing Meng, Hamada H. Mohammed, Gamal El-Din A. Abuo-Rahma, Shujie Yang, Aliasger K. Salem
Summary: Dysfunction of p53 gene and presence of MDR1 gene are associated with many malignant tumors, including endometrial cancer, and contribute to drug resistance. A new ciprofloxacin derivative, CIP2b, in combination with taxanes, showed synergistic cytotoxic effects against endometrial cancer cells with MDR1 expression and loss-of-function p53. CIP2b targets multiple pathways and enhances the effects of paclitaxel on microtubule assembly.
Article
Biochemistry & Molecular Biology
Zhipeng Fu, Tao Zhang, Zhongxia Zhou, Dongwei Kang, Lin Sun, Shenghua Gao, Srinivasulu Cherukupalli, Erik De Clercq, Christophe Pannecouque, Xinyong Liu, Peng Zhan
Summary: The newly designed DAPYs compounds demonstrated potent inhibition against HIV-1, with some showing significant activity against the K103N mutant virus. FS2 was identified as the most significant compound, showing superior potency compared to current drugs. Further optimization based on SARs and molecular modeling studies is recommended.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Shengliang Zhang, Lindsey Carlsen, Liz Hernandez Borrero, Attila A. Seyhan, Xiaobing Tian, Wafik S. El-Deiry
Summary: This article summarizes the current progress in targeting wild-type and mutant p53 for cancer therapy using biotherapeutic and biopharmaceutical methods. Strategies include boosting p53 activity, restoring p53 pathway function, targeting p53 in immunotherapy, and combination therapies.
Article
Chemistry, Multidisciplinary
Yuan Pei, Jingfeng Fu, Yunkai Shi, Mengmeng Zhang, Guanghao Luo, Xiaomin Luo, Ning Song, Tian Mi, Yaxi Yang, Jia Li, Yubo Zhou, Bing Zhou
Summary: The selective degradation of USP7 using a PROTAC has shown promising results in inhibiting the growth of p53 mutant cancer cells, providing a potential therapeutic strategy for p53 mutant cancers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Pharmacology & Pharmacy
Eduardo Garcia-Garrido, Marco Cordani, Alvaro Somoza
Summary: This study developed a gold nanoparticle modification technique for efficient delivery of Gapmer targeting mutant p53 proteins. These nanoparticles can effectively reduce mutant p53 protein levels, alter related molecular markers, and show promising results in overcoming chemoresistance to gemcitabine in pancreatic cancer treatment.
Article
Biochemistry & Molecular Biology
Hanine Hadni, Menana Elhallaoui
Summary: In this study, drug design was carried out targeting the mutations in the p53 gene. New anticancer compounds were predicted using computer simulation methods, and the predictive ability and stability of the models were tested using various validation methods. Based on molecular docking and molecular dynamics simulation results, the designed compounds showed crucial interactions with the active sites of the p53 protein. The results suggest the potential of these compounds for the treatment of colon cancer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Oncology
Jiahao Hu, Jiasheng Cao, Win Topatana, Sarun Juengpanich, Shijie Li, Bin Zhang, Jiliang Shen, Liuxin Cai, Xiujun Cai, Mingyu Chen
Summary: TP53 is a critical tumor-suppressor gene commonly mutated in human cancers, with potential oncogenic properties when mutated. Treatments for cancers with mutant p53 involve targeting mutant p53 directly, restoring wild-type functions, and exploring synthetic lethal interactions with mutant p53 for therapeutic benefits. Additionally, disrupting noncoding RNA networks may have potential synthetic lethal effects in cancers with p53 mutations.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jiajian Wang, Wenjun Liu, Lanqing Zhang, Jihong Zhang
Summary: More than 50% of cancer patients have TP53 mutation, and the highly stabilized mutant p53 protein plays a crucial role in tumorigenesis and progression. The mutation of p53 not only leads to loss-of-function and dominant-negative effects, but also promotes tumorigenesis through abnormal stability regulated by the ubiquitin-proteasome system and molecular chaperones. The accumulation of mutant p53 is mainly controlled by molecular chaperones, such as Hsp40, Hsp70, Hsp90, as well as other biomolecules like TRIM21, BAG2, and Stat3. Additionally, mutant p53 can form prion-like aggregates or complexes with other proteins, leading to its accumulation in tumor cells. Depleting mutant p53 has become a strategy for targeting mutant p53, and this review focuses on the mechanisms of mutant p53 stabilization and discusses strategies to manipulate these interconnected processes for cancer therapy.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Takatsune Shimizu, Eiji Sugihara, Hideyuki Takeshima, Hiroyuki Nobusue, Rui Yamaguchi, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Toshikazu Ushijima, Akihiro Muto, Hideyuki Saya
Summary: Mutant p53 in osteosarcoma cells does not suppress the activity of wild-type p53. Targeting mutant p53 R270C (equivalent to human R273C) has limited therapeutic potential, as it does not prevent invasion and metastasis in cells.
Review
Biochemistry & Molecular Biology
Katarzyna A. Roszkowska, Aleksandra Piecuch, Maria Sady, Zdzislaw Gajewski, Sylwia Flis
Summary: This review focuses on several novel therapeutic opportunities, including APR-246, COTI-2, SAHA, and PEITC, which can reactivate p53 or destabilize mutant p53, and discusses their significance for potential medical application.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Qiaosi Tang, Gizem Efe, Anna M. Chiarella, Jessica Leung, Maoting Chen, Taiji Yamazoe, Zhenyi Su, Jason R. Pitarresi, Jinyang Li, Mirazul Islam, Tatiana Karakasheva, Andres J. Klein-Szanto, Samuel Pan, Jianhua Hu, Shoji Natsugoe, Wei Gu, Ben Z. Stanger, Kwok-K Wong, J. Alan Diehl, Adam J. Bass, Hiroshi Nakagawa, Maureen E. Murphy, Anil K. Rustgi
Summary: Esophageal squamous cell carcinoma (ESCC) is a deadly cancer that often metastasizes to the lungs. The study investigated how the p53R175H mutation regulates metastasis in ESCC. Depletion of Trp53R172H in primary tumor cell lines led to reduced invasion and lung metastasis, with the YAP-BIRC5 axis identified as a potential mediator. Survivin, a protein encoded by BIRC5, was found to be upregulated by Trp53R172H and associated with increased metastasis in GI cancers. These findings provide new insights into mutant p53-mediated metastasis.
GENES & DEVELOPMENT
(2021)
Article
Oncology
Kate Brown, Lisa M. Miller Jenkins, Daniel R. Crooks, Deborah R. Surman, Sharlyn J. Mazur, Yuan Xu, Bhargav S. Arimilli, Ye Yang, Andrew N. Lane, Teresa W-M. Fan, David S. Schrump, W. Marston Linehan, R. Taylor Ripley, Ettore Appella
Summary: TP53 is the most frequently mutated gene in cancer, with various gain-of-function mutations. The NSC59984 compound has been found to reactivate mutant p53 in colorectal cancer cells. This study investigated the effects of NSC59984 on esophageal adenocarcinoma cells with specific p53 hot-spot mutations and demonstrated its p53-dependent effects on cellular metabolism, with greater activity in cells harboring the p53 R248W mutation.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Joseph R. Stephenson Clarke, Leon R. Douglas, Patrick J. Duriez, Dimitrios-Ilias Balourdas, Andreas C. Joerger, Raniya Khadiullina, Emil Bulatov, Matthias G. J. Baud
Summary: The tumor suppressor protein p53 is inactivated in the majority of human cancers, and the Y220C mutant is one of the most prevalent p53 mutants. This study presents the development of high-affinity small molecules to stabilize p53-Y220C, marking an important milestone in the search for effective anticancer therapies.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Mehregan Babamohamadi, Esmaeil Babaei, Burhan Ahmed Salih, Mahshid Babamohammadi, Hewa Jalal Azeez, Goran Othman
Summary: The p53 protein is a tumor suppressor that regulates various cellular processes and is closely related to cancer development. It can be used as a biomarker for tumor progression and a target for cancer treatment. This review discusses the contribution of wild-type p53 loss of function, its role in ferroptosis and targeted therapy, and challenges and solutions in p53-related drug delivery systems.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Oncology
Yen-Ting Chiang, Yi-Chung Chien, Yu-Heng Lin, Hui-Hsuan Wu, Dung-Fang Lee, Yung-Luen Yu
Summary: TP53 is a well-known tumor-suppressor gene commonly mutated in cancer, with missense mutations occurring at hotspots like p53-R175H, promoting cancer progression. Mutant p53 proteins lose wild-type functions and gain oncogenic functions, leading to enhanced proliferation, migration, invasion, and drug resistance in cancer cells. Research focuses on understanding the gain of function of p53-R175H in different cancer types and developing treatments targeting this mutation, such as small molecules to reactivate or degrade p53-R175H and immunotherapies targeting the p53-R175H-HLA complex.
Article
Chemistry, Multidisciplinary
Alan R. Healy, Douglas R. Houston, Lucy Remnant, Anne-Sophie Huart, Veronika Brychtova, Magda M. Maslon, Olivia Meers, Petr Muller, Adam Krejci, Elizabeth A. Blackburn, Borek Vojtesek, Lenka Hernychova, Malcolm D. Walkinshaw, Nicholas J. Westwood, Ted R. Hupp
Article
Biochemical Research Methods
Terry A. Gray, Nicola J. MacLaine, Caroline O. Michie, Pavia Bouchalova, Euan Murray, Jacqueline Howie, Roman Hrstka, Magdalena M. Maslon, Rudolf Nenutil, Borek Vojtesek, Simon Langdon, Larry Hayward, Charlie Gourley, Ted R. Hupp
JOURNAL OF IMMUNOLOGICAL METHODS
(2012)
Article
Biochemistry & Molecular Biology
Magdalena M. Maslon, Roman Hrstka, Borek Vojtesek, Ted R. Hupp
JOURNAL OF MOLECULAR BIOLOGY
(2010)
Article
Cell Biology
Marco M. Candeias, Laurence Malbert-Colas, Darren J. Powell, Chrysoula Daskalogianni, Magda M. Maslon, Nadia Naski, Karima Bourougaa, Fabien Calvo, Robin Fahraeus
NATURE CELL BIOLOGY
(2008)
Article
Biochemistry & Molecular Biology
R. Hrstka, R. Nenutil, A. Fourtouna, M. M. Maslon, C. Naughton, S. Langdon, E. Murray, A. Larionov, K. Petrakova, P. Muller, M. J. Dixon, T. R. Hupp, B. Vojtesek
Article
Biology
Magdalena M. Maslon, Sara R. Heras, Nicolas Bellora, Eduardo Eyras, Javier F. Caceres
Article
Biochemistry & Molecular Biology
Magdalena M. Maslon, Ulrich Braunschweig, Stuart Aitken, Abigail R. Mann, Fiona Kilanowski, Chris J. Hunter, Benjamin J. Blencowe, Alberto R. Kornblihtt, Ian R. Adams, Javier F. Caceres
Article
Cell Biology
Dasa Longman, Kathryn A. Jackson-Jones, Magdalena M. Maslon, Laura C. Murphy, Robert S. Young, Jack J. Stoddart, Nele Hug, Martin S. Taylor, Dimitrios K. Papadopoulos, Javier F. Caceres
GENES & DEVELOPMENT
(2020)
Article
Biology
Fiona Haward, Magdalena M. Maslon, Patricia L. Yeyati, Nicolas Bellora, Jan N. Hansen, Stuart Aitken, Jennifer Lawson, Alex von Kriegsheim, Dagmar Wachten, Pleasantine Mill, Ian R. Adams, Javier F. Caceres
Summary: Shuttling RNA-binding proteins play a crucial role in coordinating gene expression between the nucleus and cytoplasm. By creating a mouse model with SRSF1 protein exclusively retained in the nucleus, researchers found that this alteration led to various cellular and tissue defects, particularly in the context of ciliogenesis. This study highlights the importance of SRSF1 shuttling in reprogramming gene expression networks under high cellular demands, such as during motile ciliogenesis.
Article
Cell Biology
Jose Miguel Fernandez-Justel, Cristina Santa-Maria, Sara Martin-Virgala, Shreya Ramesh, Alberto Ferrera-Lagoa, Monica Salinas-Pena, Javier Isoler-Alcaraz, Magdalena M. Maslon, Albert Jordan, Javier F. Caceres, Maria Gomez
Summary: This study reveals the important regulatory roles of histone H1 in chromatin structure and transcription. Histone H1 prevents non-coding RNA transcription and regulates their turnover on chromatin. The loss of histone H1 leads to reduced m6A modification levels and replication-transcription conflicts.
Article
Genetics & Heredity
Alicia Gallego, Jose Miguel Fernandez-Justel, Sara Martin-Virgala, Magdalena M. Maslon, Maria Gomez
Summary: N6-methyladenosine modification (m6A) regulates RNA fate and biological processes. Slow transcription leads to preferential methylation of genes, which show specific features in their promoter regions. This study highlights the link between RNAPII velocity, chromatin structure, and m6A deposition.