Article
Oncology
Bibek Bhatta, Ishai Luz, Christian Krueger, Fanny Xueting Teo, David P. Lane, Kanaga Sabapathy, Tomer Cooks
Summary: Extracellular vesicles (EVs) released by cancer cells play a crucial role in transferring molecular information and reprogramming the tumor microenvironment. Mutations in the TP53 gene, encoding the p53 protein, lead to loss of tumor-suppressive properties and acquisition of novel functions that promote cancer growth. This study demonstrates that mutant p53 proteins can be transferred via EVs to neighboring cancer cells and immune cells, modulating them to support tumor growth.
Article
Cell Biology
Ambuja Navalkar, Ajoy Paul, Arunima Sakunthala, Satyaprakash Pandey, Amit Kumar Dey, Sandhini Saha, Sarthak Sahoo, Mohit Kumar Jolly, Tushar K. Maiti, Samir K. Maji
Summary: This study reveals that p53 can form amyloids, which disrupt the normal functions of the protein and contribute to cancer development. Targeting key molecules affected by p53 amyloid formation can reverse the oncogenic phenotype and induce apoptosis in cells.
JOURNAL OF CELL SCIENCE
(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.
Review
Oncology
Valeria Capaci, Fiamma Mantovani, Giannino Del Sal
Summary: TP53 mutations are prevalent in human cancers, with missense p53 mutants enhancing the communication among tumor cells and with the tumor stroma by influencing the cancer secretome. These activities contribute to the aggressive nature of tumors and provide potential targets for therapeutic intervention.
FRONTIERS IN ONCOLOGY
(2021)
Review
Cell Biology
Tzitzijanik Madrigal, Jesus Hernandez-Monge, Luis A. Herrera, Claudia Haydee Gonzalez-De la Rosa, Guadalupe Dominguez-Gomez, Myrna Candelaria, Fernando Luna-Maldonado, Karla G. Calderon Gonzalez, Jose Diaz-Chavez
Summary: Mutations in the DNA-binding domain of p53 can give rise to different variants with new functions, known as Gain-of-function p53 mutants. Recent studies have shown that p53 mutants regulate gene expression by unbalancing specific microRNAs levels, affecting cellular processes such as epithelial-mesenchymal transition, chemoresistance, and cell survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michela Coan, Martina Toso, Laura Cesaratto, Ilenia Rigo, Silvia Borgna, Anna Dalla Pieta, Luigi Zandona, Lorenzo Iuri, Antonella Zucchetto, Carla Piazza, Gustavo Baldassarre, Riccardo Spizzo, Milena Sabrina Nicoloso
Summary: This study explored the impact of TP53 gene mutations on the transcription of non-protein-coding genes, particularly focusing on the long non-coding RNA LINC01605. The researchers discovered that LINC01605 is directly regulated by mutant p53 and plays a role in the pro-migratory pathways of breast and ovarian cancer cell lines. The findings underscore the importance of non-coding RNAs in the network of mutant p53 in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Tzitzijanik Madrigal, Daniel Ortega-Bernal, Luis A. Herrera, Claudia Haydee Gonzalez-de la Rosa, Guadalupe Dominguez-Gomez, Elena Arechaga-Ocampo, Jose Diaz-Chavez
Summary: The p53 gene mutations have a negative effect on miRNA expression and induce cell migration and invasion. The upregulation of miR-182-5p is associated with processes such as cell migration and invasion.
Article
Cell Biology
George K. Annor, Nour Elshabassy, Devon Lundine, Don-Gerard Conde, Gu Xiao, Viola Ellison, Jill Bargonetti
Summary: The TP53 gene is frequently mutated in cancer, with missense mutations in the central DNA binding domain and less often in the C-terminal oligomerization domain. Mutant p53 R273H was found to associate with replicating DNA and promote the chromatin association of replication-associated proteins. The study showed that while mtp53 R273H can form tetramers, tetramer formation is not required for the chromatin interactions associated with gain-of-function activities.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Virology
Marcel Chris Conrady, Irina Suarez, Gergo Gogl, Desiree Isabella Frecot, Anna Bonhoure, Camille Kostmann, Alexandra Cousido-Siah, Andre Mitschler, JiaWen Lim, Murielle Masson, Thomas Iftner, Frank Stubenrauch, Gilles Trave, Claudia Simon
Summary: The study compared the structures and efficiency of ternary complex formation between oncogenic E6 proteins of closely related high-risk HPV31 and HPV16 with their cellular targets p53 and E6AP. Despite high structural similarity, 31 E6 showed an overall lower binding affinity than 16 E6, aligning with the observed lower p53 degradation potential of 31 E6.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Jinfeng Jiang, Tong Qiu, Chao Yang, Yuan Yuan, Ling Qin, Peixuan Zhang
Summary: The short G1 phase of embryonic stem cells results from the promotion of G1/S transition by MEK1/2 kinases, but it is not necessarily related to pluripotency maintenance. Inhibition of MEK1/2 kinases in naive ESCs leads to a longer G1 phase. This inhibition increases the level of reactive oxygen species (ROS) and stabilizes the p53 protein. The genetic ablation of p53 transforms the cell cycle profile of naive ESCs to that of primed ESCs.
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
Madhu Kollareddy, Luis A. Martinez
Summary: Plant-derived compounds tested in this study showed the ability to reduce mutant p53 protein levels and its important targets involved in invasion and metastasis, leading to cell proliferation inhibition. These compounds also downregulated nucleotide metabolism genes and key ETS transcription family members, suggesting a potential multi-pathway inhibition of invasion in triple-negative breast cancer.
Review
Cell Biology
Eduardo Alvarado-Ortiz, Karen Griselda de la Cruz-Lopez, Jared Becerril-Rico, Miguel Angel Sarabia-Sanchez, Elizabeth Ortiz-Sanchez, Alejandro Garcia-Carranca
Summary: Frequent p53 mutations not only abolish tumor suppressor capacities but also confer various gain-of-function activities that impact key pathways in tumor development and progression. The effects of these mutations on proliferation, migration, metabolic reprogramming, and immune evasion constitute major driving forces for human tumors. The interaction of mutp53 with molecules such as AMPK and SREBP1 leads to metabolic reprogramming and favors anabolic pathways in cancer cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Elmira Roshani Asl, Davoud Rostamzadeh, Pascal H. G. Duijf, Sahar Mafi, Behnaz Mansoori, Shirin Barati, William C. Cho, Behzad Mansoori
Summary: TP53 is the most frequently mutated gene in human cancer, encoding the tumor suppressor protein p53. Mutations in TP53 gene impair p53 function, alter intracellular signaling pathways, and promote cancer development. Recent evidence suggests that p53 mutations also affect the tumor microenvironment (TME), composed of various cell types, and influence cancer progression by fine-tuning the inflammatory TME and cell fate reprogramming. Understanding how TP53 mutations reshape TME can provide insights for therapeutic strategies against cancer.
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)