Review
Cell Biology
Julian M. Rozenberg, Olga S. Rogovaya, Gerry Melino, Nickolai A. Barlev, Alexander Kagansky
Summary: p63 and p73 cooperate in genome stability surveillance, with specific interactors contributing to transcriptional repression and spindle assembly checkpoint for p73, and mRNA processing and splicing regulation for p63. This analysis reveals the diversification of RNA and DNA specific functions within the p53 family.
Article
Multidisciplinary Sciences
Alyssa M. Klein, Lynn Biderman, David Tong, Bita Alaghebandan, Sakina A. Plumber, Helen S. Mueller, Anne van Vlimmeren, Chen Katz, Carol Prives
Summary: This study suggests that MDM2 and MDMX may play a p53-independent role in maintaining cell-cycle progression by affecting the activity of E2F family members and p73, making them a potential target of interest in cancers lacking wild-type p53.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Kyra Laubach, Jin Zhang, Xinbin Chen
Summary: The p53 family of tumor suppressors, including p53, p63, and p73, play critical roles in various biological processes such as cell cycle arrest, apoptosis, differentiation, development, multiciliogenesis, and fertility. This review focuses on the roles of p53, p63, and p73 in lipid and iron metabolism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Rui Qiao, Mengmeng Wei, Hui Chen, Xianhong Zhang, Jie Zhang, Liyang Gao, Haijun Ma, Yujiong Wang, Le Li
Summary: Cancer cells alter their metabolism to support biogenesis, proliferation, and survival. The glucose-associated pentose phosphate pathway (PPP) plays a crucial role in cancer cell proliferation. TAp73 activates 6-phosphogluconate dehydrogenase (6PGD) to produce ribulose 5-phosphate (Ru5P) and NADPH, which counteracts reactive oxygen species and protects cells from apoptosis. Additionally, overexpression of 6PGD rescues the proliferation and tumorigenic ability of TAp73-deficient cells.
MOLECULAR CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Sandeep Kaur, Manabu Kurokawa
Summary: Apoptosis is a crucial process in maintaining cellular balance and development in the ovarian reserve. While a large number of oocytes are generated in the fetal ovary, most of them undergo apoptosis before birth. During puberty, primordial follicles develop into mature follicles, but only one dominant follicle is selected for ovulation, while smaller ones undergo apoptosis. The molecular mechanism of oocyte death is still not fully understood, despite extensive studies. This review discusses the roles of apoptosis regulators and the transcription factor p63 in oocyte death and survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Kiyohiro Ando, Akira Nakagawara
Summary: The RUNX family plays a crucial role in neural crest cell differentiation and may also be involved in neuroblastoma tumorigenesis. Its function in tumor development can vary depending on the specific context, including the response to chemotherapy. In primary neuroblastomas, RUNX3 acts as a tumor suppressor, while RUNX1 regulates cell proliferation in a dual manner influenced by genetic and epigenetic factors, including MYCN. This review focuses on the mechanism through which the RUNX family regulates neurotrophin receptors (Trk family) associated with neuroblastoma aggressiveness, as well as their potential involvement in functional alterations of the p53 family members in neuroblastoma tumorigenesis. Understanding the contribution of the RUNX family to neuroblastoma tumorigenesis is crucial for future molecular-based therapies.
Article
Genetics & Heredity
Julia Wallmeier, Diana Bracht, Hessa S. Alsaif, Gerard W. Dougherty, Heike Olbrich, Sandra Cindric, Mark Dzietko, Christoph Heyer, Norbert Teig, Charlotte Thiels, Eissa Faqeih, Aqeela Al-Hashim, Sameena Khan, Ibrahim Mogarri, Mohammed Almannai, Wadha Al Otaibi, Fowzan S. Alkuraya, Cordula Koerner-Rettberg, Heymut Omran
Summary: TP73, a member of the TP53 family of transcription factors, has been found to cause mucociliary clearance disorder, possibly due to a defect in multiciliated cell differentiation.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Oncology
Yuanzheng Yang, Zhanglong Peng, Elsa R. Flores, Eugenie S. Kleinerman
Summary: Outcomes for patients with osteosarcoma have remained stagnant for more than 3 decades, and the search for novel therapeutic agents is crucial. This study shows that Pramlintide, an FDA-approved drug for type 2 diabetes, may have potential efficacy against osteosarcoma by interfering with tumor glycolysis and leading to decreased cell growth and increased cell death. Injection of Pramlintide into osteosarcoma tumor nodules resulted in significantly smaller tumors, indicating its potential as a novel therapeutic approach for relapsed osteosarcoma patients.
Review
Biochemistry & Molecular Biology
Ignacija Vlasic, Andela Horvat, Ana Tadijan, Neda Slade
Summary: Metastatic melanoma, a highly aggressive tumor, is often characterized by mutations in the MAPK pathway, particularly in the protein kinase BRAF. However, resistance to BRAF inhibitors is a major obstacle in melanoma treatment, with the reactivation of MAPK or PI3K/AKT pathways and the involvement of the p53 pathway contributing to acquired resistance. In melanoma, the canonical tumor suppressor p53 is frequently inactivated through various mechanisms. The TP53 gene and its family members TP63 and TP73 encode multiple protein isoforms with diverse functions in tumorigenesis. Some p53 isoforms are expressed in melanoma cells and have been shown to play specific roles in proliferation, survival, metastasis, invasion, migration, and treatment response. Particularly, p53 isoforms involved in acquired resistance to MAPK inhibitors present potential therapeutic targets to overcome resistance in melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Gongwei Wu, Noriaki Yoshida, Jihe Liu, Xiaoyang Zhang, Yuan Xiong, Tayla B. Heavican-Foral, Elisa Mandato, Huiyun Liu, Geoffrey M. Nelson, Lu Yang, Renee Chen, Katherine A. Donovan, Marcus K. Jones, Mikhail Roshal, Yanming Zhang, Ran Xu, Ajit J. Nirmal, Salvia Jain, Catharine Leahy, Kristen L. Jones, Kristen E. Stevenson, Natasha Galasso, Nivetha Ganesan, Tiffany Chang, Wen-Chao Wu, Abner Louissaint, Lydie Debaize, Hojong Yoon, Paola Dal Cin, Wing C. Chan, Shannan J. Ho Sui, Samuel Y. Ng, Andrew L. Feldman, Steven M. Horwitz, Karen Adelman, Eric S. Fischer, Chun-Wei Chen, David M. Weinstock, Myles Brown
Summary: Gene fusions involving TP63 play a crucial role in lymphomas and have a significant impact on prognosis. TP63 fusions coordinate the recruitment of two epigenetic modifying complexes, resulting in therapeutic vulnerability to EZH2 inhibition. Targeting EZH2 with valemetostat shows promising results in treating lymphoma harboring TP63 fusions.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Teruyuki Kobayashi, Tomoki Makino, Kotaro Yamashita, Takuro Saito, Koji Tanaka, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Eiichi Morii, Hidetoshi Eguchi, Yuichiro Doki
Summary: Mutations in the p53 gene are found in 90% of esophageal squamous cell carcinoma (ESCC) patients, and APR-246 shows potential as a therapeutic agent to overcome chemo-resistance by inducing apoptosis through restoring transcriptional ability of mutant p53. APR-246 treatment induces significant apoptosis in ESCC cell lines with p53 missense mutations by upregulating p73 and Noxa via ROS induction, and the combination with chemotherapy enhances antitumor effects.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Jingshan Tong, Xiao Tan, Suisui Hao, Kaylee Ermine, Xinyan Lu, Zhaojin Liu, Anupma Jha, Jian Yu, Lin Zhang
Summary: Targeting cyclin-dependent kinases (CDKs) has shown promising therapeutic potential against cancer. A recent study reveals that selective CDK4/6 inhibitors induce Death Receptor 5 (DR5) via p73, leading to increased sensitivity of colorectal cancer cells to therapy-induced apoptosis. This finding provides valuable insights into the anticancer mechanisms of CDKIs and their potential clinical applications in colorectal cancer.
Article
Oncology
Jolynn Zu Lin Ong, Rui Yokomori, Regina Wan Ju Wong, Tze King Tan, Ryuzo Ueda, Takashi Ishida, Shinsuke Iida, Takaomi Sanda
Summary: This study reveals that TP73 is highly activated under the control of a super-enhancer in ATL cells, contributing to cell proliferation and DNA damage response. Moreover, the deletion of TP73 exons 2-3 in primary ATL cases enhances cell proliferation and mutational burden.
Review
Biochemistry & Molecular Biology
Bi-He Cai, Yun-Chien Hsu, Fang-Yu Yeh, Yu-Rou Lin, Rui-Yu Lu, Si-Jie Yu, Jei-Fu Shaw, Ming-Han Wu, Yi-Zhen Tsai, Ying-Chen Lin, Zhi-Yu Bai, Yu-Chen Shih, Yi-Chiang Hsu, Ruo-Yu Liao, Wei-Hsin Kuo, Chao-Tien Hsu, Ching-Feng Lien, Chia-Chi Chen
Summary: p53 family members p53, p63, and p73 have tumor suppressor function, but p53 has a high mutation rate in cancers causing loss of its function. This review discusses drug therapies for nonsense and missense mutations in p53, and proposes p63 and p73 activators as potential anti-cancer drugs to replace mutant p53. Strategies to improve the response of these activators, particularly for p53 gain-of-function mutants, are also discussed.
Article
Oncology
Xin Wang, Ana P. Kutschat, Joana Aggrey-Fynn, Feda H. Hamdan, Rondell P. Graham, Alexander Q. Wixom, Yara Souto, Swetlana Ladigan-Badura, Jennifer A. Yonkus, Amro M. Abdelrahman, Roberto Alva-Ruiz, Jochen Gaedcke, Philipp Stroebel, Robyn Laura Kosinsky, Florian Wegwitz, Patrick Hermann, Mark J. Truty, Jens T. Siveke, Stephan A. Hahn, Elisabeth Hessmann, Steven A. Johnsen, Zeynab Najafova
Summary: The lack of molecular stratification approaches and targeted therapy is a major hurdle in applying precision oncology to pancreatic cancer. This study aimed to identify molecular and epigenetic signatures of a specific subclass of pancreatic ductal adenocarcinoma (PDAC) and validate their application for patient stratification and therapy monitoring. By analyzing gene expression and epigenome mapping data, the researchers identified subtype-specific enhancer regions and successfully confirmed the validity of enhancer RNA (eRNA) detection as a histologic approach for patient stratification. This study provides proof-of-concept that single-cell level detection of subtype-specific epigenetic changes is possible in complex primary tumor material.
MOLECULAR CANCER RESEARCH
(2023)
Article
Biophysics
Rosita Primavera, Martina Di Francesco, Antonella De Cola, Vincenzo De Laurenzi, Donatella Paolino, Matteo Ciancaioni, Maria Carafa, Christian Celia, Carmine Di Ilio, Antonio Di Stefano, Massimo Fresta, Marcello Locatelli, Luisa Di Marzio
COLLOIDS AND SURFACES B-BIOINTERFACES
(2015)
Article
Multidisciplinary Sciences
Stefano Bartesaghi, Vincenzo Graziano, Sara Galavotti, Nick V. Henriquez, Joanne Betts, Jayeta Saxena, A. Deli, Anna Karlsson, L. Miguel Martins, Melania Capasso, Pierluigi Nicotera, Sebastian Brandner, Vincenzo De Laurenzi, Paolo Salomoni
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Cell Biology
V. Iorio, M. Festa, A. Rosati, M. Hahne, C. Tiberti, M. Capunzo, V. De Laurenzi, M. C. Turco
CELL DEATH & DISEASE
(2015)
Review
Cell Biology
N. Allocati, M. Masulli, C. Di Ilio, V. De Laurenzi
CELL DEATH & DISEASE
(2015)
Article
Cell Biology
A. De Cola, S. Volpe, M. C. Budani, M. Ferracin, R. Lattanzio, A. Turdo, D. D'Agostino, E. Capone, G. Stassi, M. Todaro, C. Di Ilio, G. Sala, M. Piantelli, M. Negrini, A. Veronese, V. De laurenzi
CELL DEATH & DISEASE
(2015)
Article
Cell Biology
M. d'Avenia, R. Citro, M. De Marco, A. Veronese, A. Rosati, R. Visone, S. Leptidis, L. Philippen, G. Vitale, A. Cavallo, A. Silverio, C. Prota, P. Gravina, A. De Cola, E. Carletti, G. Coppola, S. Gallo, G. Provenza, E. Bossone, F. Piscione, M. Hahne, L. J. De Windt, M. C. Turco, V. De laurenzi
CELL DEATH & DISEASE
(2015)
Article
Multidisciplinary Sciences
Alessandra Rosati, Anna Basile, Raffaella D'Auria, Morena d'Avenia, Margot De Marco, Antonia Falco, Michelina Festa, Luana Guerriero, Vittoria Iorio, Roberto Parente, Maria Pascale, Liberato Marzullo, Renato Franco, Claudio Arra, Antonio Barbieri, Domenica Rea, Giulio Menichini, Michael Hahne, Maarten Bijlsma, Daniela Barcaroli, Gianluca Sala, Fabio Francesco di Mola, Pierluigi di Sebastiano, Jelena Todoric, Laura Antonucci, Vincent Corvest, Anass Jawhari, Matthew A. Firpo, David A. Tuveson, Mario Capunzo, Michael Karin, Vincenzo De Laurenzi, Maria Caterina Turco
NATURE COMMUNICATIONS
(2015)
Article
Cell Biology
Veronica Esposito, Carlo Baldi, Pio Zeppa, Michelina Festa, Luana Guerriero, Morena d'Avenia, Massimiliano Chetta, Fulvio Zullo, Vincenzo De Laurenzi, Maria Caterina Turco, Alessandra Rosati, Maurizio Guida
JOURNAL OF CELLULAR PHYSIOLOGY
(2017)
Article
Oncology
Gabriele Corda, Gianluca Sala, Rossano Lattanzio, Manuela Iezzi, Michele Sallese, Giorgia Fragassi, Alessia Lamolinara, Hasan Mirza, Daniela Barcaroli, Sibylle Ermler, Elisabete Silva, Hemad Yasaei, Robert F. Newbold, Paola Vagnarelli, Marcella Mottolese, Pier Giorgio Natali, Letizia Perracchio, Jelmar Quist, Anita Grigoriadis, Pierfrancesco Marra, Andrew N. Tutt, Mauro Piantelli, Stefano Iacobelli, Vincenzo De Laurenzi, Arturo Sala
JOURNAL OF PATHOLOGY
(2017)
Article
Cell Biology
Albino Carrizzo, Antonio Damato, Mariateresa Ambrosio, Antonia Falco, Alessandra Rosati, Mario Capunzo, Michele Madonna, Maria C. Turco, James L. Januzzi, Vincenzo De Laurenzi, Carmine Vecchione
CELL DEATH & DISEASE
(2016)
Review
Biochemistry & Molecular Biology
L. Galluzzi, J. M. Bravo-San Pedro, I. Vitale, S. A. Aaronson, J. M. Abrams, D. Adam, E. S. Alnemri, L. Altucci, D. Andrews, M. Annicchiarico-Petruzzelli, E. H. Baehrecke, N. G. Bazan, M. J. Bertrand, K. Bianchi, M. V. Blagosklonny, K. Blomgren, C. Borner, D. E. Bredesen, C. Brenner, M. Campanella, E. Candi, F. Cecconi, F. K. Chan, N. S. Chandel, E. H. Cheng, J. E. Chipuk, J. A. Cidlowski, A. Ciechanover, T. M. Dawson, V. L. Dawson, V. De laurenzi, R. De Maria, K-M Debatin, N. Di Daniele, V. M. Dixit, B. D. Dynlacht, W. S. El-Deiry, G. M. Fimia, R. A. Flavell, S. Fulda, C. Garrido, M-L Gougeon, D. R. Green, H. Gronemeyer, G. Hajnoczky, J. M. Hardwick, M. O. Hengartner, H. Ichijo, B. Joseph, P. J. Jost, T. Kaufmann, O. Kepp, D. J. Klionsky, R. A. Knight, S. Kumar, J. J. Lemasters, B. Levine, A. Linkermann, S. A. Lipton, R. A. Lockshin, C. Lopez-Otin, E. Lugli, F. Madeo, W. Malorni, J-C Marine, S. J. Martin, J-C Martinou, J. P. Medema, P. Meier, S. Melino, N. Mizushima, U. Moll, C. Munoz-Pinedo, G. Nunez, A. Oberst, T. Panaretakis, J. M. Penninger, M. E. Peter, M. Piacentini, P. Pinton, J. H. Prehn, H. Puthalakath, G. A. Rabinovich, K. S. Ravichandran, R. Rizzuto, C. M. Rodrigues, D. C. Rubinsztein, T. Rudel, Y. Shi, H-U Simon, B. R. Stockwell, G. Szabadkai, S. W. Tait, H. L. Tang, N. Tavernarakis, Y. Tsujimoto, Tom Vanden Berghe, P. Vandenabeele, A. Villunger, E. F. Wagner, H. Walczak, E. White, W. G. Wood, J. Yuan, Z. Zakeri, B. Zhivotovsky, G. Melino, G. Kroemer
CELL DEATH AND DIFFERENTIATION
(2015)
Article
Biotechnology & Applied Microbiology
Nerino Allocati, Michele Masulli, Piero Del Boccio, Damiana Pieragostino, Domenico D'Antonio, David Sheehan, Carmine Di Ilio
FOLIA MICROBIOLOGICA
(2014)
Article
Biochemical Research Methods
Simona D'Aguanno, Daniela Barcaroli, Claudia Rossi, Mirco Zucchelli, Domenico Ciavardelli, Claudio Cortese, Antonella De Cola, Silvia Volpe, Daniela D'Agostino, Matilde Todaro, Giorgio Stassi, Carmine Di Ilio, Andrea Urbani, Vincenzo De Laurenzi
JOURNAL OF PROTEOME RESEARCH
(2014)
Article
Biochemistry & Molecular Biology
Ilaria Cela, Maria Concetta Cufaro, Maurine Fucito, Damiana Pieragostino, Paola Lanuti, Michele Sallese, Piero Del Boccio, Adele Di Matteo, Nerino Allocati, Vincenzo De Laurenzi, Luca Federici
Summary: The role of nucleostemin in acute myeloid leukemia (AML) is unclear. Using a proteomics approach, researchers found that silencing nucleostemin in AML cells had effects on DNA repair and increased DNA damage rates, indicating its potential importance in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)