About this Research Topic
Ubiquitination, a post-translational modification process, involves the covalent attachment of a small protein, ubiquitin, to lysine residues on target proteins. This intricately orchestrated process requires the sequential action of three enzymes: ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). These enzymes collaborate to transfer ubiquitin from E1 to E2 and ultimately, E3 ligases facilitate the attachment of ubiquitin to target substrates. The nature of ubiquitination and the structure of ubiquitin chains dictate diverse fates for proteins, encompassing degradation, localization, activity regulation, and signal transduction involvement. Ubiquitination plays a pivotal role in cellular homeostasis, participating in virtually all cellular processes such as cell cycle control, signal transduction, gene expression regulation, DNA repair, and cellular response mechanisms. Predominantly, ubiquitination signals for protein degradation through the proteasome pathway. However, non-degradative roles of ubiquitination also exist, which include modulation of protein activity and regulation of protein-protein interactions.
In the realm of immunology, ubiquitination is central to the regulation of immune responses and the maintenance of immune system homeostasis. Dysregulation in the ubiquitination process is linked to the pathogenesis of various immune diseases, including autoimmune disorders, inflammatory responses, and immune deficiencies. For example, ubiquitination modulates T cell receptor (TCR) signaling pathways, affecting T cell activation and differentiation, with aberrations potentially leading to autoimmune diseases. Moreover, ubiquitination regulates the production and release of inflammatory cytokines, such as TNF-α and IL-1β, with its dysregulation associated with the progression of inflammatory diseases.
Within the tumor microenvironment, ubiquitination exerts complex influences on tumor cell survival, proliferation, and apoptosis. It also affects immune evasion by modulating the activity of immune cells like T cells and the polarization of macrophages. Imbalances in ubiquitination not only promote tumor growth and metastasis but also alter the sensitivity of tumors to immunotherapies, including immune checkpoint inhibitors. Key signaling pathways regulated by ubiquitination, such as NF-κB and Wnt/β-catenin, play crucial roles in oncogenesis. Anomalies in the ubiquitination process, such as overexpression or mutations in certain E3 ligases, can enhance the proliferative, survival, and anti-apoptotic capacities of tumor cells, while also impacting immune cells within the tumor microenvironment, thereby facilitating tumor immune evasion.
In summary, ubiquitination is a versatile and crucial post-translational modification that regulates various cellular and immunological processes. Its role in the immune system and the tumor microenvironment underscores its significance in disease pathogenesis and the potential for therapeutic intervention. However, the mechanisms underlying ubiquitination in disease contexts remain to be fully elucidated. Keeping abreast of research developments on ubiquitination will facilitate the discovery of novel therapeutic strategies and the development of targeted drugs.
This Research Topic focuses on the intricate role of ubiquitination, such as immune regulation, drug resistance, disease pathogenesis, and remodeling of the tumor microenvironment. It aims to highlight how ubiquitination impacts disease progression and treatment approaches, offering insights into potential therapies and enhancing our knowledge of disease mechanisms through a detailed study of its diverse functions.
We welcome mini-reviews, systematic reviews, clinical trials, and original research articles covering, but not limited to, the following topics:
1. Explore the regulation of immune cell functions through ubiquitination in non-cancerous diseases, providing insights into how ubiquitination influences immune responses across various pathological conditions.
2. Investigate changes in ubiquitination processes within the tumor immune microenvironment and their implications for tumor progression, focusing on how ubiquitination mediates the complex interactions between tumor cells and the immune system.
3. Uncover new mechanisms involved in the regulation of ubiquitination processes, offering innovative perspectives on the molecular underpinnings of ubiquitin-mediated regulation in immunology.
4. Present the latest advancements in ubiquitination research, including novel discoveries that enhance our current understanding and open new avenues for investigation.
5. New drugs that target the ubiquitination pathway.
6. The potential utility of ubiquitination levels as biomarkers for disease diagnosis, immunotherapy response, and prognosis.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
In the realm of immunology, ubiquitination is central to the regulation of immune responses and the maintenance of immune system homeostasis. Dysregulation in the ubiquitination process is linked to the pathogenesis of various immune diseases, including autoimmune disorders, inflammatory responses, and immune deficiencies. For example, ubiquitination modulates T cell receptor (TCR) signaling pathways, affecting T cell activation and differentiation, with aberrations potentially leading to autoimmune diseases. Moreover, ubiquitination regulates the production and release of inflammatory cytokines, such as TNF-α and IL-1β, with its dysregulation associated with the progression of inflammatory diseases.
Within the tumor microenvironment, ubiquitination exerts complex influences on tumor cell survival, proliferation, and apoptosis. It also affects immune evasion by modulating the activity of immune cells like T cells and the polarization of macrophages. Imbalances in ubiquitination not only promote tumor growth and metastasis but also alter the sensitivity of tumors to immunotherapies, including immune checkpoint inhibitors. Key signaling pathways regulated by ubiquitination, such as NF-κB and Wnt/β-catenin, play crucial roles in oncogenesis. Anomalies in the ubiquitination process, such as overexpression or mutations in certain E3 ligases, can enhance the proliferative, survival, and anti-apoptotic capacities of tumor cells, while also impacting immune cells within the tumor microenvironment, thereby facilitating tumor immune evasion.
In summary, ubiquitination is a versatile and crucial post-translational modification that regulates various cellular and immunological processes. Its role in the immune system and the tumor microenvironment underscores its significance in disease pathogenesis and the potential for therapeutic intervention. However, the mechanisms underlying ubiquitination in disease contexts remain to be fully elucidated. Keeping abreast of research developments on ubiquitination will facilitate the discovery of novel therapeutic strategies and the development of targeted drugs.
This Research Topic focuses on the intricate role of ubiquitination, such as immune regulation, drug resistance, disease pathogenesis, and remodeling of the tumor microenvironment. It aims to highlight how ubiquitination impacts disease progression and treatment approaches, offering insights into potential therapies and enhancing our knowledge of disease mechanisms through a detailed study of its diverse functions.
We welcome mini-reviews, systematic reviews, clinical trials, and original research articles covering, but not limited to, the following topics:
1. Explore the regulation of immune cell functions through ubiquitination in non-cancerous diseases, providing insights into how ubiquitination influences immune responses across various pathological conditions.
2. Investigate changes in ubiquitination processes within the tumor immune microenvironment and their implications for tumor progression, focusing on how ubiquitination mediates the complex interactions between tumor cells and the immune system.
3. Uncover new mechanisms involved in the regulation of ubiquitination processes, offering innovative perspectives on the molecular underpinnings of ubiquitin-mediated regulation in immunology.
4. Present the latest advancements in ubiquitination research, including novel discoveries that enhance our current understanding and open new avenues for investigation.
5. New drugs that target the ubiquitination pathway.
6. The potential utility of ubiquitination levels as biomarkers for disease diagnosis, immunotherapy response, and prognosis.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Keywords: Ubiquitination, tumor cells, immune regulation, Disease Development, Disease Progression, Disease Prognosis, Tumor Microenvironment
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
