Review
Cell Biology
Linbin Zhou, Danny Siu-Chun Ng, Jason C. Yam, Li Jia Chen, Clement C. Tham, Chi Pui Pang, Wai Kit Chu
Summary: This review summarizes recent findings on the impact of post-translational modifications (PTMs) on the functions of retinoblastoma protein (pRb). PTMs on pRb play crucial roles in cell cycle regulation, cell survival, and differentiation, and altered PTMs can lead to anomalies in cell proliferation and tumorigenesis. Understanding the post-translational modulation of pRb could facilitate the development of novel therapeutic strategies for various human diseases.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Review
Clinical Neurology
Carolina Alquezar, Shruti Arya, Aimee W. Kao
Summary: Post-translational modifications play a crucial role in regulating tau protein function, including phosphorylation and acetylation. While these modifications may regulate protein function under normal conditions, they can be hijacked in disease states. Limited understanding exists on how these modifications impact tau protein, but studies indicate their critical role in localization, interactions, and other aspects.
FRONTIERS IN NEUROLOGY
(2021)
Review
Mathematical & Computational Biology
Shahin Ramazi, Javad Zahiri
Summary: Posttranslational modifications (PTMs) involve modifications to amino acid side chains in proteins after biosynthesis, affecting various aspects of protein functions. Disruptions in PTMs can lead to diseases, emphasizing the need for computational methods to predict PTMs. High-throughput experimental methods for PTM discovery are laborious, prompting the exploration of computational tools and databases to advance research in this area.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2021)
Review
Multidisciplinary Sciences
Ji Min Lee, Henrik M. Hammaren, Mikhail M. Savitski, Sung Hee Baek
Summary: Post-translational modifications (PTMs) on specific amino acids control the stability of target proteins. These PTM-regulated degrons act as signals for protein degradation or stabilization. This review summarizes the current knowledge of PTM-mediated protein stability regulation to enhance the identification of novel drug targets.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Ivana Samarzija
Summary: The specific functional form of a protein is mostly achieved through dynamic interactions of many enzymes in post-translational modifications, which cells widely use to respond to stimuli, regulate transcription, and maintain proteostasis. Post-translational modifications play important roles in driving prostate cancer, particularly in regulating protein activity at the level of post-translational modifications.
Review
Cell Biology
Chunhua Yang, Mengna Wei, Yanpu Zhao, Zhanyi Yang, Mengyao Song, Jia Mi, Xiaoyong Yang, Geng Tian
Summary: Post-translational modifications (PTMs) in pancreatic beta cells play crucial roles in insulin secretion and have significant implications for diabetes mellitus development. This article summarizes the major PTMs occurring in beta cells and their impact on insulin secretion, providing valuable insights into the understanding of insulin secretion mechanisms and potential therapeutic targets for diabetes from the perspective of protein PTMs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yanfeng Wang, Feng Wang
Summary: Post-translational modifications like ubiquitination play crucial roles in regulating biological processes in eukaryotes, with DUBs being key enzymes that control ubiquitin-related pathways. Dysregulation of DUBs can lead to various diseases. Phosphorylation is the most extensively studied post-translational modification of DUBs, influencing their function and activity.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Behavioral Sciences
Jaquelini B. Canever, Ericks Sousa Soares, Nubia C. P. de Avelar, Helena I. Cimarosti
Summary: This review provides an overview of the pathophysiological roles of alpha-synuclein in Parkinson's disease and discusses various post-translational modifications that are implicated in its functions. It also highlights the potential of alpha-synuclein PTMs as biomarkers for PD.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Bethany C. Taylor, Nicolas L. Young
Summary: Histone post-translational modifications (PTMs) play a crucial role in regulating the genome by storing and transmitting complex signals about the genome state. Different PTM sites on the same histone molecule or nucleosome work in concert, supported by 'readers' structures, to transduce signals in specific cellular contexts.
BIOCHEMICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Annachiara Tesoriere, Alberto Dinarello, Francesco Argenton
Summary: STAT3 is a crucial transcription factor regulating cell growth and proliferation by controlling gene transcription; it plays significant roles in cancer progression, with different post-translational modifications having opposite effects in different cellular models; the extensive results from various studies show that post-translational modifications drastically alter STAT3 activities, necessitating further analysis to fully elucidate its multifaceted functions.
Review
Biochemistry & Molecular Biology
Siyi Zhang, Tingting Zhou, Zhuo Wang, Fei Yi, Chunlu Li, Wendong Guo, Hongde Xu, Hongyan Cui, Xiang Dong, Jingwei Liu, Xiaoyu Song, Liu Cao
Summary: Faithful DNA replication is crucial for cell survival and inheritance, but damage can lead to replication stalling and DNA lesions. Post-translational modifications of PCNA regulate DNA synthesis and damage tolerance to maintain genomic stability. Dysregulation of PCNA PTMs can result in DNA breaks, affecting cell response and causing mutations.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Developmental Biology
Jessica Ispada, Aldcejam Martins da Fonseca Junior, Otavio Luiz Ramos Santos, Camila Bruna de Lima, Erika Cristina dos Santos, Vinicius Lourenco da Silva, Fernanda Nascimento Almeida, Saul de Castro Leite, Pablo Juan Ross, Marcella Pecora Milazzotto
Summary: This study investigates the relationship between metabolic differences and histone post-translational modifications in bovine embryos, finding distinct patterns of H3K9ac and H3K9me3 between embryos with different development kinetics. The differences in H3K9ac were explained by metabolic pathways influencing acetyl-CoA production.
Review
Endocrinology & Metabolism
Monique D. Appelman, Suzanne W. van der Veen, Saskia W. C. van Mil
Summary: The FXR nuclear receptor is activated by bile acids and plays a crucial role in controlling gene expression related to bile acid, lipid, glucose, and amino acid metabolism. Post-translational modifications of FXR, such as phosphorylation, SUMOylation, and acetylation, have functional consequences on DNA binding, ligand binding, and transcription of target genes, and may be involved in cholestatic and metabolic disorders.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Adam Albanese, Leonard A. Daly, Daniela Mennerich, Thomas Kietzmann, Violaine See
Summary: The hypoxia signaling pathway allows cells to adapt to decreased oxygen availability, with HIF transcription factors playing a crucial role in inducing the expression of hypoxia-regulated genes. In addition to hydroxylation, other post-translational modifications of HIF also play a crucial role in altering its localization, stability, and activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Ana Gonzalez-Garcia, Antonio Garrido, Ana C. Carrera
Summary: Genetic alterations in the PI3-kinase/PTEN pathway are common in cancer cells. Current efforts to treat PTEN-dependent tumors mainly focus on PI3-kinase inhibition, but modulating PTEN post-translational modifications could provide alternative therapeutic strategies.
Article
Cell Biology
Francesca Zonta, Christian Borgo, Camila Paz Quezada Meza, Ionica Masgras, Andrea Rasola, Mauro Salvi, Lorenzo A. Pinna, Maria Ruzzene
Summary: CK2, an overexpressed Ser/Thr protein kinase in many cancers, plays a crucial role in the uncontrolled proliferation, motility, and survival of cancer cells. This study reveals that both CK2 alpha and alpha' isoforms contribute to cell proliferation, survival, and tumorigenicity, with a prominent role for CK2 alpha in tumor metabolism.
Article
Chemistry, Medicinal
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. Pinna
Summary: CK2, a protein kinase with pleiotropic functions, is implicated in global human pathologies, particularly cancer. Selective inhibitors like CX4945 and GO289 show promise in controlling the CK2-dependent phosphoproteome.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Claudio D'Amore, Mauro Salvi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Christian Borgo, Claudio D'Amore, Luca Cesaro, Stefania Sarno, Lorenzo A. Pinna, Maria Ruzzene, Mauro Salvi
Summary: CK2 is a constitutively active protein kinase that plays a crucial role in maintaining phosphorylation levels for various substrates, supporting important biological functions. However, its activity must be carefully regulated to prevent pathological consequences, especially in diseases like cancer, chronic inflammation, and neurodegeneration. Understanding the regulation of CK2 is essential for potential therapeutic interventions in related diseases.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Respiratory System
Claudio D'Amore, Christian Borgo, Mauro Salvi
Summary: The functional recovery of F508del-CFTR is related to the post-translational modifications (PTMs) of CFTR, but regulating the PTM code is not essential for therapeutic approaches.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Cell Biology
Mauro Salvi, Christian Borgo, Lorenzo A. Pinna, Maria Ruzzene
Summary: The newly developed compound SGC-CK2-1, which is more selective than other CK2 inhibitors, has shown poor efficacy in reducing cell growth in different cancer cell lines, raising questions about the anticancer efficacy of CX-4945, the commonly used clinical-grade CK2 inhibitor.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Christian Borgo, Claudio D'Amore, Valeria Capurro, Valeria Tomati, Elvira Sondo, Federico Cresta, Carlo Castellani, Nicoletta Pedemonte, Mauro Salvi
Summary: The advent of Trikafta has revolutionized the treatment of cystic fibrosis patients with the most common misfolding mutation, F508del-CFTR. However, there is still room for improvement in its efficacy, especially in rare CFTR mutations. By targeting the misfolding detection machinery, the combination of Trikafta with a drug like TAK-243 shows promising results in improving CFTR function, including in rare CF-causing mutations.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Claudio D'Amore, Christian Borgo, Valentina Bosello Travain, Mauro Salvi
Summary: Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene, which encodes a chloride ion channel responsible for regulating chloride transport. Recent research has identified post-translational modifications of CFTR and suggested modulating these modifications as a potential therapeutic strategy. Using a siRNA library, we identified enzymes whose downregulation increases the stability and function of the F508del-CFTR mutant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Eleanor L. Atkinson, Jessica Iegre, Claudio D'Amore, Paul Brear, Mauro Salvi, Marko Hyvonen, David R. Spring
Summary: In this study, an iterative cycle of enzymatic assays, X-ray crystallography, molecular modelling and cellular assays was used to develop a functionalisable chemical probe for the investigation of CK2α/β PPI. The lead peptide, P8C9, showed successful binding to CK2α at the PPI site, and it was found to be easily synthesizable and functionalisable. The peptide also exhibited high stability in serum and had potential for further optimization.
CHEMICAL COMMUNICATIONS
(2022)