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
Biochemistry & Molecular Biology
Emine Guven-Maiorov, Nozomi Sakakibara, Roshini M. Ponnamperuma, Kun Dong, Hector Matar, Kathryn E. King, Wendy C. Weinberg
Summary: Members of the p53 family, including p53, p63, and p73, share high homology but can be activated differently and have distinct roles in different tissues. By predicting interaction partners and modeling their 3D structures, we gain insights into the functions and mechanisms of these family members.
MOLECULAR CARCINOGENESIS
(2022)
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
Multidisciplinary Sciences
Saptaparna Mukherjee, Martino Maddalena, YiQing Lu, Sebastien Martinez, Nishanth Belugali Nataraj, Ashish Noronha, Sansrity Sinha, Katie Teng, Victoria Cohen-Kaplan, Tamar Ziv, Sharathchandra Arandkar, Ori Hassin, Rishita Chatterjee, Anna-Chiara Pirona, Michal Shreberk-Shaked, Anat Gershoni, Yael Aylon, Zvulun Elazar, Yosef Yarden, Daniel Schramek, Moshe Oren
Summary: The p53R273H mutant interacts with SQSTM1/p62 and promotes cancer cell migration and invasion in a p62-dependent manner by driving the proteasomal degradation of cell junction-associated proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biology
Julian M. Rozenberg, Svetlana Zvereva, Aleksandra Dalina, Igor Blatov, Ilya Zubarev, Daniil Luppov, Alexander Bessmertnyi, Alexander Romanishin, Lamak Alsoulaiman, Vadim Kumeiko, Alexander Kagansky, Gerry Melino, Carlo Ganini, Nikolai A. Barlev
Summary: During oncogenesis, cells undergo unrestricted proliferation, altering tissue homeostasis and possibly due to dysregulation of p53 family proteins p63 and p73. While p63 and p73 can compensate for loss of p53 in some cases, their overlap with p53 functions is strongest in regulating p53-dependent gene expression. Surprisingly, p73 is rarely lost or mutated in cancers, with its inactive isoforms often overexpressed and promoting cancer growth by repressing cell death mediated by p73.
Article
Engineering, Biomedical
Adria Sales, Valia Khodr, Paul Machillot, Line Chaar, Laure Fourel, Amaris Guevara-Garcia, Elisa Migliorini, Corinne Albiges-Rizo, Catherine Picart
Summary: By studying the presentation of matrix-bound BMPs on films of controlled stiffness, it was found that different BMP members have specific effects on cell adhesion and differentiation of skeletal progenitors. This response involves certain BMP receptors and beta chain integrins and is dependent on the stiffness of the substrate.
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
Oncology
Ana Tadijan, Francesca Precazzini, Nikolina Hanzic, Martina Radic, Nicolo Gavioli, Ignacija Vlasic, Petar Ozretic, Lia Pinto, Lidija Skreblin, Giulia Barban, Neda Slade, Yari Ciribilli
Summary: The study found that melanoma cells express a wide array of p53 and p73 isoforms, with &UDelta;160p53a showing the most variability. It was demonstrated for the first time that &UDelta;160p53a can be recruited on chromatin and stimulate proliferation and migration. Vemurafenib-resistant melanoma cells exhibited increased expression of potentially pro-oncogenic isoforms and decreased expression of tumor-suppressive isoforms, suggesting a role of p53 family isoforms in melanoma aggressiveness.
Article
Biochemistry & Molecular Biology
Tirthankar Koley, Sanghati Roy Chowdhury, Tushar Kushwaha, Manoj Kumar, Krishna Kishore Inampudi, Punit Kaur, Tej Pal Singh, Hector Viadiu, Abdul Samath Ethayathulla
Summary: In this study, the molecular details of p73 recognizing response elements (REs) were investigated. The crystal structure and molecular dynamics simulations revealed that p73 recognizes specific nucleotides in different p53 promoter sequences and forms a unique tetramer with each natural promoter sequence through the interaction of key residues. Additionally, the structural features of DNA and the spacing between half-sites influence p73's function.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Cell Biology
Julian M. Rozenberg, Svetlana Zvereva, Alexandra Dalina, Igor Blatov, Ilya Zubarev, Daniil Luppov, Alexander Bessmertnyi, Alexander Romanishin, Lamak Alsoulaiman, Vadim Kumeiko, Alexander Kagansky, Gerry Melino, Nikolai A. Barlev
Summary: p73 plays a dual role in cancer progression, acting as a tumor suppressor by regulating apoptosis in response to genotoxic stress and as an oncoprotein by promoting an immunosuppressive environment and immune cell differentiation in the tumor microenvironment.
Article
Cell Biology
Daniel Feng, Peng Gao, Nathalie Henley, Marion Dubuissez, Nan Chen, Louis-Philippe Laurin, Virginie Royal, Vincent Pichette, Casimiro Gerarduzzi
Summary: SMOC2 is highly expressed in RCC tissue and is associated with shorter patient survival. SMOC2 induces EMT in kidney epithelial cells, promoting RCC metastasis. Mechanistically, SMOC2 activates EMT through the integrin beta 3, FAK, and paxillin pathway. In vivo studies demonstrate that SMOC2 overexpression leads to increased tumor growth and metastatic potential.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Matilde Fregni, Yari Ciribilli, Joanna E. Zawacka-Pankau
Summary: Lung cancer remains the leading cause of cancer-related mortality globally, with metastatic disease patients having a low survival rate. EGFR and TP53 are common driver mutations, with EGFR-positive patients commonly treated with tyrosine kinase inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Lucija Mijanovic, Igor Weber
Summary: Dictyostelium amoebae adhere to extracellular material using similar mechanisms to metazoan cells, despite lacking integrins. The adhesion complexes in free-living amoeboid cells have evolved to enable less specific interactions with diverse materials encountered in their natural habitat.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Qiong Wu, Fangfang Liu, Mengmeng Ge, Kyle Vaughn Laster, Lixiao Wei, Ruijuan Du, Ming Jiang, Jing Zhang, Yafei Zhi, Guoguo Jin, Simin Zhao, Dong Joon Kim, Zigang Dong, Kangdong Liu
Summary: The study demonstrates the important role of BRD4 in promoting the progression of esophageal squamous cell carcinoma (ESCC), suppressing BRD4 can downregulate the expression of RCC2, thereby inhibiting the proliferation of ESCC cells.
Article
Medicine, General & Internal
Daria M. Potashnikova, Aleena A. Saidova, Anna V. Tvorogova, Alexandra S. Anisimova, Alexandra Yu Botsina, Elena Yu Vasilieva, Leonid B. Margolis
Summary: The study found that the presence of fibronectin can significantly increase CTL adhesiveness in atherosclerosis patients, and the expression levels of integrin-coding mRNAs also increase accordingly.
FRONTIERS IN MEDICINE
(2022)
Article
Multidisciplinary Sciences
Anna Maria Lena, Valerio Rossi, Susanne Osterburg, Artem Smirnov, Christian Osterburg, Marcel Tuppi, Angela Cappello, Ivano Amelio, Volker Doetsch, Massimo De Felici, Francesca Gioia Klinger, Margherita Annicchiarico-Petruzzelli, Herbert Valensise, Gerry Melino, Eleonora Candi
Summary: The transcription factor p63 plays a crucial role in regulating cellular responses related to epithelial and oocyte biology. By replacing p63 alpha with p63 beta in a mouse model, researchers demonstrated that this change affects ovary development, mimicking the characteristics of human primary ovary insufficiency.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Oleg Shuvalov, Alexandra Daks, Olga Fedorova, Alexey Petukhov, Nickolai Barlev
Summary: This review discusses the role of metabolic reprogramming in malignant cells and highlights the key features of metabolic reprogramming and plasticity associated with different stages of cancer. The successful usage of metabolic drugs in anticancer therapy is also provided with new promising targets for the development of new metabolic drugs.
Editorial Material
Oncology
Ivano Amelio, Gerry Melino, Arnold J. Levine
MOLECULAR ONCOLOGY
(2021)
Review
Cell Biology
Oleg Shuvalov, Alyona Kizenko, Alexey Petukhov, Olga Fedorova, Alexandra Daks, Nikolai Barlev
Summary: CTAs are proteins strictly expressed in male reproductive tissues under normal conditions, but are frequently re-expressed in neoplastic tissues upon malignisation, affecting tumor cell growth, migration, and invasion. SEMGs, major components of human seminal fluid, play a role in sperm motility and capacitation, and their re-expression in different malignancies including breast cancer is known, but their functional properties in cancer cells remain largely unknown.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Olga Fedorova, Anastasia Gudovich, Alexandra Daks, Ekaterina Baidyuk, Oleg Shuvalov, Alexey Petukhov, Sergey Parfenyev, Alena Kizenko, Nikolai A. Barlev
Summary: Autophagy is a cellular program induced by nutrient and energy deprivation, and is important for cancer cells to survive under unfavorable conditions. The E3 ligase Pirh2 is shown to regulate autophagy in non-small cell lung cancer cells, with knockdown resulting in decreased expression of autophagy-related genes and increased sensitivity to doxorubicin treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biology
Emanuele Panatta, Carlotta Zampieri, Gerry Melino, Ivano Amelio
Summary: Mutations in the TP53 gene affect half of all human cancers, impairing the regulation of several cellular functions. Recent studies have described additional mechanisms for p53-mediated tumor suppression, including regulation of alternative cell death modalities, cell metabolism, and its emerging role in RNA stability.
Article
Biochemistry & Molecular Biology
Olga Fedorova, Alexandra Daks, Sergey Parfenyev, Oleg Shuvalov, Sofia Netsvetay, Julia Vasileva, Anastasia Gudovich, Vasilii Golotin, Oleg Semenov, Alexey Petukhov, Ekaterina Baiduik, Nurken Berdigaliyev, Eugene M. Tulchinsky, Nikolai A. Barlev
Summary: The text delves into the role of autophagy in cellular processes, exploring the relationship between autophagy and DNA damage, as well as the mechanisms through which tumor cells and breast cancer cells handle anticancer drugs and drug resistance.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Carlotta Zampieri, Emanuele Panatta, Vincenzo Corbo, Alessandro Mauriello, Gerry Melino, Ivano Amelio
Summary: This study reveals the molecular mechanism of drug-tolerant phenotype caused by p53 mutants in pancreatic cancer. Mutant p53 fine-tunes chromatin accessibility and orchestrates transcriptional activity, influencing the phenotypic evolution of pancreatic cancer, and strongly correlates with drug response and aggressive phenotype.
MOLECULAR ONCOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Konstantin G. Shevchenko, Irina S. Garkushina, Francesco Canfarotta, Sergey A. Piletsky, Nickolai A. Barlev
Summary: Molecularly imprinted polymers (MIPs) are synthetic polymeric structures that selectively recognize target molecules. They can exceed the affinity and selectivity of natural antibodies and can be fabricated against any target molecule. MIPs can be used for controlled release of therapeutic payloads, making them a potential novel class of therapeutics in medicine.
Article
Biology
Alessio Butera, Micaela Roy, Carlotta Zampieri, Eleonora Mammarella, Emanuele Panatta, Gerry Melino, Angelo D'Alessandro, Ivano Amelio
Summary: The lipid metabolism plays a crucial role in cancer pathogenesis, and the tumor suppressor protein p53 is involved in cell metabolism. By analyzing pancreatic ductal adenocarcinoma cells, researchers discovered that p53 depletion significantly affects the lipidome, particularly the class of lysophospholipids. Lysophospholipids can function as signaling molecules and instruct the cancer microenvironment and immunity.
Review
Biochemistry & Molecular Biology
Nadezhda M. Kolyasnikova, Nikolay B. Pestov, Jeanne P. Sanchez-Pimentel, Nikolay A. Barlev, Aidar A. Ishmukhametov
Summary: The idea of using viruses to destroy malignant cells has been around for a long time, but it has only gained significant attention in recent years due to the successful use of oncolytic viruses in treating advanced melanoma. This review focuses on the history of oncolytic viruses in Russia and discusses recent biotechnological advancements and their potential applications in aggressive tumors like glioblastoma or pancreatic cancer. The use of virus-derived vectors armed with prodrug-converting enzymes and the improvement of oncotropism through conjugation with biopolymers and nanoformulations are also explored.
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
(2023)
Article
Cell Biology
Emanuele Panatta, Alessio Butera, Eleonora Mammarella, Consuelo Pitolli, Alessandro Mauriello, Marcel Leist, Richard A. Knight, Gerry Melino, Ivano Amelio
Summary: Gene-environment interactions can lead to perturbations in the epigenome that contribute to cancer development. In this study, we found that the tumor suppressor p53 plays a role in maintaining genomic integrity by regulating the levels of the universal methyl donor S-adenosylmethionine (SAM). Loss of p53 results in disruptions in DNA methylation, leading to chromosomal abnormalities and replication stress associated with R-loops. Insufficient levels of SAM contribute to the inability of p53-deficient cells to cope with these disruptions.
Article
Biology
Daria Kriger, Ksenia Novitskaya, Giomar Vasileva, Ekaterina Lomert, Nikolai D. D. Aksenov, Nikolai A. A. Barlev, Dmitri Tentler
Summary: ACTN4 may influence the resistance of cancer cells to topoisomerase II inhibitors and affect the efficiency of DNA double strand breaks repair.
Article
Biology
Emanuele Panatta, Alessio Butera, Ivana Celardo, Marcel Leist, Gerry Melino, Ivano Amelio
Summary: Nuclear organization and architecture are crucial for genomic integrity, epigenetic regulation, and gene expression. This study reveals that loss of p53 is associated with increased expression of nuclear pore complex and nuclear lamina members, and directly regulates the transcription of Lamin B1.
Editorial Material
Medicine, Research & Experimental
Alessio Butera, Lena Smirnova, Elisa Ferrando-May, Thomas Hartung, Thomas Brunner, Marcel Leist, Ivano Amelio
Summary: Human health is influenced by both genetics and environment. Different responses can be observed in groups of individuals exposed to the same environmental factors. The concept of gene-environment interactions is still not well defined, but examples of these interactions driving disease development are provided in this article. The cellular epigenome is suggested to hold the key to unravel these complex layers of regulation. Developing a method to decode epigenetic information could provide quantitative measures of disease risk, similar to the concept of an epigenetic clock for estimating biological age.
EMBO MOLECULAR MEDICINE
(2023)
