The Role of Ubiquitin Ligases in Regulating Immune Cell Functions: Cbl and Beyond

  • 282

    Total views and downloads

About this Research Topic

Submission deadlines

  1. Manuscript Summary Submission Deadline 31 January 2025 | Manuscript Submission Deadline 30 April 2025

  2. This Research Topic is still accepting articles.

Background

Ubiquitin-mediated post-translational regulation of proteins is an essential mechanism that influences protein structure, function, and stability. Among the E3 ubiquitin ligases, Cbl is of particular interest in the context of signal transduction in T cells and NK cells, where it serves as a key regulator of receptor-linked signaling pathways that control cell activation. In addition to Cbl, other E3 ubiquitin ligases, such as GRAIL, Itch, and members of the TRIM family, play significant roles in immune cell regulation by promoting the ubiquitination and subsequent degradation of critical proteins involved in immune responses.

Cbl promotes the proteasomal degradation of TCR/CD3 subunits in T cells and the degradation of protein kinases Fyn and Lck, which are essential for cell activation. It also regulates the degradation of the scaffold protein LAT in both T cells and NK cells and participates in various regulatory mechanisms at the immunological synapse. Other ubiquitin ligases, such as Itch and GRAIL, contribute to immune tolerance and regulation by targeting distinct substrates, while TRIM family members are involved in antiviral immunity and innate immune signaling.

Recent findings suggest that Cbl mediates the ubiquitination and degradation of C3G via CrkII during early T cell activation, which may also have implications for NK cell signaling. Similarly, E3 ligases such as Itch and GRAIL play roles in maintaining immune homeostasis and preventing autoimmunity by controlling the degradation of key signaling proteins.
This Research Topic covers significant contributions related to Cbl and other ubiquitin ligases in the context of T cell and NK cell function. Selected manuscripts will analyze the roles of the distinct Cbl proteins, as well as GRAIL, Itch, TRIM family members, and other relevant ubiquitin ligases, in the regulation of immune cell responses. Additional manuscripts will review the mechanisms of regulation, including post-translational modifications such as phosphorylation or ubiquitination, or interactions with a wide range of binding partners that lead to conformational changes, proteasomal degradation, or alterations in subcellular localization and enzymatic activity of target proteins.

Additional topics will focus on the biochemical roles of Cbl-b, c-Cbl, GRAIL, Itch, and other E3 ubiquitin ligases in T lymphocyte and NK cell function. These molecules play important and non-redundant roles in T cell activation and immune synapse formation. Manuscripts will describe the role of Cbl and related ligases in promoting the proteasomal degradation of proteins critical for regulating cell activation, including TCR/CD3 subunits, Fyn and Lck protein tyrosine kinases, LAT scaffold protein, and the C3G guanine-nucleotide-exchange factor, as well as proteins targeted by other E3 ligases.

Given their roles in modulating immune responses and their manageable impact on autoimmunity, Cbl and other ubiquitin ligases are being investigated as potential targets for cancer immunotherapy. This collection brings together leading experts from various disciplines to review the latest discoveries and offer new perspectives on the contributions of Cbl isoforms and other ubiquitin ligases to biochemical processes and signaling events in immune cells, and their impact on the host immune response. Specific themes of this Research Topic include, but are not limited to:

• Cbl and related ubiquitin ligases: structure-function relationships
• Ubiquitin-mediated regulation of signal transduction in lymphoid cells
• Regulation of T cell and NK cell responses by Cbl, GRAIL, Itch, and TRIM family ligases
• Ubiquitination and proteasomal degradation in immune cells
• Mechanisms of cell transformation by Cbl and other oncogenic ubiquitin ligases
• Ubiquitin ligases as targets in cancer immunotherapy
• Involvement of ubiquitin ligases in autoimmunity

We are currently accepting Original research, Systematic review, Methods, Review, Mini review, Perspective, Clinical trials, Case report, Brief research report, and Opinion.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

  • Brief Research Report
  • Case Report
  • Classification
  • Clinical Trial
  • Editorial
  • General Commentary
  • Hypothesis and Theory
  • Methods
  • Mini Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Keywords: Cbl; ubiquitin; signal transduction; proteasomal degradation; T cell; NK cell; cancer immunotherapy; autoimmunity; oncogene

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.

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and it falls under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

    In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

Manuscripts can be submitted to this Research Topic via the main journal or any other participating journal.

Impact

  • 282Topic views
View impact