Review
Cell Biology
Dana L. Woodstock, Morgan A. Sammons, Martin Fischer
Summary: p53 and p63, as transcription factors, regulate both shared and unique target genes to exert their tumor suppressive or oncogenic effects. The previous notion of strict competition between the two siblings needs to be reevaluated, as they can also collaborate towards a common goal.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Manisha R. Patil, Anand Bihari
Summary: The protein p53 has been extensively studied for the past 43 years since its discovery. It acts as a guardian of the genome by regulating cell division and preventing the growth of cells, thereby inhibiting tumor development. This article traces the history of p53 protein and discusses how its function has evolved over time.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Haixia Ji, Wenzhe Wang, Xia Li, Xiaoying Han, Xinyu Zhang, Juan Wang, Changxiao Liu, Luqi Huang, Wenyuan Gao
Summary: This review discusses the role of the p53 gene in regulating ferroptosis, primarily through influencing metabolic networks and signaling pathways that affect tumor cell sensitivity to ferroptosis. This has important implications for further understanding the role of p53 in tumor ferroptosis and developing new strategies for cancer treatment.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Alanna B. Chan, Gian Carlo G. Parico, Jennifer L. Fribourgh, Lara H. Ibrahim, Michael J. Bollong, Carrie L. Partch, Katja A. Lamia
Summary: Disruption of circadian rhythms can increase the risk of various cancers. Mutations in the CRY2 gene found in human cancers have been shown to accelerate cell growth in mouse fibroblasts expressing high levels of c-MYC. These mutations also have divergent effects on circadian rhythms and interaction with SCFFBXL3.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Alberta Palazzo, Hector Hernandez-Vargas, Delphine Goehrig, Jean-Jacques Medard, David Vindrieux, Jean-Michel Flaman, David Bernard
Summary: Cancer cells arising from senescent cells display more aggressive features and resistance to drugs. A molecular signature of these cells can serve as a prognostic marker for several human cancers.
Review
Cell Biology
Cen Zhang, Juan Liu, Jianming Wang, Tianliang Zhang, Dandan Xu, Wenwei Hu, Zhaohui Feng
Summary: Hypoxia is crucial in solid tumors, with HIF and p53 signaling pathways playing key roles in regulating cellular responses to hypoxia. The interplay between hypoxia and p53 pathways can impact cancer progression, with p53 regulating hypoxia and HIF signaling in various ways, while mutant p53 can promote cancer progression through interaction with hypoxia and HIF signaling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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.
Review
Biotechnology & Applied Microbiology
Taylor P. Berke, Simon H. Slight, Salman M. Hyder
Summary: The tumor suppressor protein p53 plays a crucial role in preventing cancer. Mutations in the p53 gene are associated with various cancers. Reactivating mutant p53 protein and controlling the progression of triple-negative breast cancer (TNBC) through the use of non-toxic natural compounds is recommended.
ONCOTARGETS AND THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Seung Un Seo, Seon Min Woo, Shin Kim, Jong-Wook Park, Hyun-Shik Lee, Young-Seuk Bae, Sang Hyun Kim, Seung-Soon Im, Ji Hae Seo, Kyoung-Jin Min, Taeg Kyu Kwon
Summary: Inhibition of cathepsin K enhances oxaliplatin-induced apoptosis by increasing OTUB1 phosphorylation, promoting p53 stabilization, and upregulating Bax expression, leading to decreased tumor size. There is a strong correlation between phosphorylation of OTUB1(Ser16) and p53/Bax expression in human renal clear cell carcinoma tissues.
Review
Medicine, General & Internal
Dehua Yu, Zhiyuan Xu, Xiangdong Cheng, Jiangjiang Qin
Summary: miRNAs play a crucial role in regulating the MDMX-p53 network and have significant implications in human cancer. Restoring the activity of p53 by negatively regulating MDMX provides a new approach for cancer treatment.
JOURNAL OF EVIDENCE BASED MEDICINE
(2021)
Review
Cell Biology
Md Ataur Rahman, Moon Nyeo Park, Md Hasanur Rahman, Md Mamunur Rashid, Rokibul Islam, Md Jamal Uddin, Md Abdul Hannan, Bonglee Kim
Summary: p53, the key tumor suppressor protein, plays a significant role in regulating various biological processes, including energy metabolism, cell cycle, apoptosis, and more. Autophagy, a crucial cellular process, is involved in maintaining cellular homeostasis. The relationship between p53 and autophagy is complex and not completely understood, as p53 can both inhibit and activate autophagy depending on its cellular localization and mode of action. Understanding the interaction between p53 and autophagy is important for cancer treatment and management.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rinka Nakajima, Reika Deguchi, Hideyuki Komori, Lin Zhao, Yaxuan Zhou, Mashiro Shirasawa, Arlene Angelina, Yasuko Goto, Fumiya Tohjo, Kengo Nakahashi, Kimi Nakata, Ritsuko Iwanaga, Andrew P. Bradford, Keigo Araki, Tomoko Warita, Kiyoshi Ohtani
Summary: The TFDP1 gene codes for the heterodimeric partner DP1 of the transcription factor E2F, which plays important roles in cell proliferation. Over-expression of E2F1 and inactivation of the tumor suppressor pRB induce TFDP1 gene expression, suggesting that TFDP1 is a target of E2F. Serum stimulation also induces TFDP1 expression, but with different kinetics compared to other E2F target genes. The TFDP1 promoter contains E2F1-responsive elements, and mutation of GC-rich elements reduces E2F1 responsiveness. Knockdown of DP1 expression enhances ARF gene expression, indicating that TFDP1 activation by deregulated E2F may function as a feedback mechanism to suppress deregulated E2F activity and maintain normal cell growth.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ukjin Kim, Kwang Seok Kim, Jong-Kuk Park, Hong -Duck Um
Summary: The p53 tumor suppressor protein can regulate cell functions either as a transcription factor or by interaction with other proteins. The interaction between p53 and p21 was found to influence the transcriptional activity of p53. Furthermore, p21 was shown to play a role in regulating the expression of endogenous p53 targets.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Zaofeng Yang, Marianne M. M. Lee, Michael K. Chan
Summary: The study demonstrates that Pos3Aa crystals can serve as an efficient vehicle for delivering proteins into cells, reversing the inactivation of potential cancer therapeutics and making them more sensitive to chemotherapy drugs.
Article
Biochemistry & Molecular Biology
Yue Zhang, Zhifang Xu, Wen Wen, Zhichao Liu, Chao Zhang, Ming Li, Fengping Hu, Shi Wei, Sejong Bae, Jiangbing Zhou, Runhua Liu, Lizhong Wang
Summary: In this study, it was found that miR-3622a-3p inhibited cell migration and invasion in human prostate cancer, while miR-3622b-3p promoted cell proliferation, migration, and invasion. miR-3622 regulated the p53-downstream gene network to control apoptosis and the cell cycle. AIFM2 was identified as a direct target of miR-3622b-3p and responsible for miR-3622 knockout-induced apoptosis. Additionally, miR-3622 knockout inhibited the epithelial-mesenchymal transition involved in prostate cancer metastasis through upregulation of vimentin.
Article
Biochemistry & Molecular Biology
David A. Jans, Kylie M. Wagstaff
Summary: Ivermectin, originally approved for parasitic indications, has gained attention in recent years as a potential antiviral agent. Studies have shown its ability to inhibit a range of viruses, including HIV-1, dengue, Zika, and SARS-CoV-2. Numerous clinical trials are currently underway, with preliminary results indicating clinical benefits.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Veronica Di Antonio, Giorgio Palu, Gualtiero Alvisi
Summary: The replication of HCMV genome involves a complex interaction between host and viral products, with ppUL44 playing a crucial role in viral replication by forming protein complexes in the nucleus and cytoplasm. Our study using fluorescence and bioluminescence resonance energy transfer assays revealed the importance of ppUL44 dimerization and interaction with pUL54, providing insights for potential therapeutic targets and antiviral drug discovery.
Article
Virology
Hanieh Ghassabian, Federico Falchi, Martina Timmoneri, Beatrice Mercorelli, Arianna Loregian, Giorgio Palu, Gualtiero Alvisi
Summary: Human cytomegalovirus (HCMV) is a major cause of severe diseases in immunocompromised individuals. Existing drugs have limitations, leading to the exploration of new targets for therapeutic intervention. Inhibition of viral protein-protein interactions, particularly targeting dimerization of HCMV DNA polymerase processivity factor ppUL44, shows promise as a potential new class of HCMV inhibitors.
Article
Multidisciplinary Sciences
Ilaria Dorigatti, Enrico Lavezzo, Laura Manuto, Constanze Ciavarella, Monia Pacenti, Caterina Boldrin, Margherita Cattai, Francesca Saluzzo, Elisa Franchin, Claudia Del Vecchio, Federico Caldart, Gioele Castelli, Michele Nicoletti, Eleonora Nieddu, Elisa Salvadoretti, Beatrice Labella, Ludovico Fava, Simone Guglielmo, Mariateresa Fascina, Marco Grazioli, Gualtiero Alvisi, Maria Cristina Vanuzzo, Tiziano Zupo, Reginetta Calandrin, Vittoria Lisi, Lucia Rossi, Ignazio Castagliuolo, Stefano Merigliano, H. Juliette T. Unwin, Mario Plebani, Andrea Padoan, Alessandra R. Brazzale, Stefano Toppo, Neil M. Ferguson, Christl A. Donnelly, Andrea Crisanti
Summary: A study in Vo', Italy, conducted two mass swab testing campaigns in February and March 2020, followed by serological surveys in May and November. The findings show a seroprevalence of 3.5% in May and indicate that the majority of positive sera in May still reacted against at least one antigen in November. Analysis of household members revealed a Susceptible-Infectious Transmission Probability of 26.0%, with limited impact of contact tracing on epidemic suppression.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Azadeh Safarchi, Shadma Fatima, Zahra Ayati, Fatemeh Vafaee
Summary: The global pandemic of COVID-19 has led to a serious public health and economic crisis and has united efforts worldwide to develop diagnostics, vaccines, and therapeutics. Various interdisciplinary studies and techniques have been employed to aid in overcoming the challenges posed by the disease.
CELL AND BIOSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Kieran F. Scott, Timothy J. Mann, Shadma Fatima, Mila Sajinovic, Anshuli Razdan, Ryung Rae Kim, Adam Cooper, Aflah Roohullah, Katherine J. Bryant, Kasuni K. Gamage, David G. Harman, Fatemeh Vafaee, Garry G. Graham, W. Bret Church, Pamela J. Russell, Qihan Dong, Paul de Souza
Summary: The article provides an overview of the research history of phospholipase A(2) (PLA(2)) enzymes, emphasizing their role in inflammatory responses. It points out the lack of success in research on group IIA sPLA(2) and the absence of clinically approved targeted drugs. Future research efforts need to focus on the characteristics of enzyme function and develop functionally-selective and isoform-selective inhibitors.
Article
Cell Biology
Sundy N. Y. Yang, Belinda Maher, Chunxiao Wang, Kylie M. Wagstaff, Johanna E. Fraser, David A. Jans
Summary: This study identifies two drugs that can inhibit the replication of dengue virus and other flaviviruses by directly binding to a viral protein.
Article
Cell Biology
Sujata B. Walunj, Manisha M. Dias, Chhaminder Kaur, Kylie M. Wagstaff, Vishakha Dey, Caroline Hick, Swati Patankar, David A. Jans
Summary: This study reveals the potential of IMP alpha proteins from Plasmodium falciparum and Toxoplasma gondii as targets for small molecule inhibitors. Through high-throughput screening, compounds that inhibit the binding of P. falciparum IMP alpha to a P. falciparum NLS were identified and shown to limit the growth of both P. falciparum and T. gondii. These findings suggest that apicomplexan IMP alpha proteins could be therapeutic targets for the development of novel agents against these neglected parasitic diseases.
Article
Biochemistry & Molecular Biology
Reena Ghildyal, Michael N. Teng, Kim C. Tran, John Mills, Marco G. Casarotto, Philip G. Bardin, David A. Jans
Summary: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in infants and the elderly. The study identified protein kinase CK2 as a regulator of RSV matrix (M) protein's distribution between the nucleus and cytoplasm. Serine (S) 95 and threonine (T) 205 were found to be key CK2 sites. These findings provide insights for developing antiviral strategies targeting CK2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Katarzyna A. Gajewska, John M. Haynes, David A. Jans
Summary: IPO13 plays a key role in neuronal differentiation of embryonic stem cells, primarily through nuclear transport of the key regulator Pax6.
Article
Cell Biology
Katarzyna A. Gajewska, David A. Jans, Kylie M. Wagstaff
Summary: The cellular response to environmental stresses is dependent on the trafficking of stress-signalling molecules, which is mediated by nuclear transporters. IPO13 is a unique bidirectional transporter that can translocate between the nucleus and cytoplasm under stress. Its activity affects cell fate decision during stress.
Article
Pharmacology & Pharmacy
Gualtiero Alvisi, Elisabetta Manaresi, Emily M. Cross, Mikayla Hoad, Nasim Akbari, Silvia Pavan, Daryl Ariawan, Gloria Bua, Gayle F. Petersen, Jade Forwood, Giorgio Gallinella
Summary: Human parvovirus B19 (B19V) is a major pathogen that primarily infects human progenitor cells in bone marrow. The non-structural protein NS1 plays a crucial role in viral replication and host gene expression. This study identified a specific sequence of amino acids as the nuclear localization signal responsible for NS1 nuclear import, which was found to be dependent on importin alpha/beta and energy. Ivermectin, an antiparasitic drug that interferes with importin alpha/beta-dependent nuclear import, inhibited NS1 nuclear accumulation and viral replication.
ANTIVIRAL RESEARCH
(2023)
Review
Virology
Matteo Centazzo, Lara Manganaro, Gualtiero Alvisi
Summary: Human immunodeficiency virus 1 (HIV-1) viral protease (PR) is not only involved in virion maturation but also has the ability to cleave host cell proteins. It targets proteins involved in translation, cell survival, and innate antiviral responses, thereby promoting viral production, immune evasion, and viral dissemination. However, there is still much to be discovered about the modulation of host cell function by HIV-1 PR.
Article
Cell Biology
MengJie Hu, Marie A. A. Bogoyevitch, David A. A. Jans
Summary: Respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants, immunosuppressed adults, and the elderly worldwide. The RSV matrix protein (M) is responsible for inducing mitochondrial dysfunction and increased reactive oxygen species (ROS) generation during RSV infection. Mutations in M impair virus production and affect the expression of genes encoding mitochondrial proteins.
Article
Computer Science, Artificial Intelligence
A. K. M. Azad, Shadma Fatima, Alexander Capraro, Shafagh A. Waters, Fatemeh Vafaee
Summary: COVID-CDR is an online platform that prioritizes drug combinations with potential synergistic effects, providing various information for understanding drug-pair similarity scores and other related information. It offers a systematic approach for clinicians and researchers to make decisions in treating COVID-19.