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Ubiquitin and Ubiquitin-Like Molecules in Cancer
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Ubiquitin and Ubiquitin-Like Molecules in Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 14016

Special Issue Editor

Dr. Giuseppe Servillo

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Perugia, Perugia, Italy
Interests: molecular oncology; HOPS/TMUB1; ubiquitin-like modifier; epigenetic gene expression; liver regeneration; apoptosis and cell cycle in cancer research; cell biology; circadian rhythms

Special Issue Information

Dear Colleagues,

Cell homeostasis is fundamental for ensuring appropriate responses to cell stress. The balance of the amount of protein in a cell is an established mechanism that guarantees the right level at the right time. The complex system of protein homeostasis plays a crucial role in cancer. Many proteins are involved in controlling the balance of protein degradation and stability. This fine-regulating mechanism is fundamental for orchestrating vital pathways such as the cell cycle, apoptosis, DNA damage and repair, and signal transduction in cell growth. Many molecules are involved in the ubiquitin–proteosome machinery, but the mechanisms are not always clear. The role of protein degradation and stability will be investigated in different aspects of cancer pathology.

This Special Issue is focused on the role played by ubiquitin-system proteins (E1–E3), deubiquitination and modifiers in cancer. It will include original articles that more deeply elucidate specific aspects of protein homeostasis in tumorigenesis. It will also consider therapeutic aspects related to the ubiquitin–proteosome machinery and relevant pharmacological advancements.

Dr. Giuseppe Servillo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • cancer
  • ubiquitin
  • ubiquitin–proteosome machinery
  • ubiquitin ligases (E3s)
  • DUBs
  • ubiquitin-like (UBL)

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Published Papers (4 papers)

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Review

16 pages, 853 KiB  
Review
Interfering with the Ubiquitin-Mediated Regulation of Akt as a Strategy for Cancer Treatment
by Elena Paccosi, Alessio Balzerano and Luca Proietti-De-Santis
Int. J. Mol. Sci. 2023, 24(3), 2809; https://doi.org/10.3390/ijms24032809 - 1 Feb 2023
Cited by 8 | Viewed by 2563
Abstract
The serine/threonine kinase Akt modulates the functions of numerous substrates, many of them being involved in cell proliferation and growth, metabolism, angiogenesis, resistance to hypoxia and migration. Akt is frequently deregulated in many types of human cancers, its overexpression or abnormal activation being [...] Read more.
The serine/threonine kinase Akt modulates the functions of numerous substrates, many of them being involved in cell proliferation and growth, metabolism, angiogenesis, resistance to hypoxia and migration. Akt is frequently deregulated in many types of human cancers, its overexpression or abnormal activation being associated with the increased proliferation and survival of cancer cells. A promising avenue for turning off the functionality of Akt is to either interfere with the K63-linked ubiquitination that is necessary for Akt membrane recruitment and activation or increase the K48-linked polyubiquitination that aims to target Akt to the proteasome for its degradation. Recent evidence indicates that targeting the ubiquitin proteasome system is effective for certain cancer treatments. In this review, the functions and roles of Akt in human cancer will be discussed, with a main focus on molecules and compounds that target various elements of the ubiquitination processes that regulate the activation and inactivation of Akt. Moreover, their possible and attractive implications for cancer therapy will be discussed. Full article
(This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Molecules in Cancer)
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16 pages, 649 KiB  
Review
A New Potential Therapeutic Target for Cancer in Ubiquitin-Like Proteins—UBL3
by Hengsen Zhang, Bin Chen, A. S. M. Waliullah, Shuhei Aramaki, Yashuang Ping, Yusuke Takanashi, Chi Zhang, Qing Zhai, Jing Yan, Soho Oyama, Tomoaki Kahyo and Mitsutoshi Setou
Int. J. Mol. Sci. 2023, 24(2), 1231; https://doi.org/10.3390/ijms24021231 - 8 Jan 2023
Cited by 1 | Viewed by 2895
Abstract
Ubiquitin-like proteins (Ubls) are involved in a variety of biological processes through the modification of proteins. Dysregulation of Ubl modifications is associated with various diseases, especially cancer. Ubiquitin-like protein 3 (UBL3), a type of Ubl, was revealed to be a key factor in [...] Read more.
Ubiquitin-like proteins (Ubls) are involved in a variety of biological processes through the modification of proteins. Dysregulation of Ubl modifications is associated with various diseases, especially cancer. Ubiquitin-like protein 3 (UBL3), a type of Ubl, was revealed to be a key factor in the process of small extracellular vesicle (sEV) protein sorting and major histocompatibility complex class II ubiquitination. A variety of sEV proteins that affects cancer properties has been found to interact with UBL3. An increasing number of studies has implied that UBL3 expression affects cancer cell growth and cancer prognosis. In this review, we provide an overview of the relationship between various Ubls and cancers. We mainly introduce UBL3 and its functions and summarize the current findings of UBL3 and examine its potential as a therapeutic target in cancers. Full article
(This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Molecules in Cancer)
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Figure 1

29 pages, 7374 KiB  
Review
The Four Homeostasis Knights: In Balance upon Post-Translational Modifications
by Stefania Pieroni, Marilena Castelli, Danilo Piobbico, Simona Ferracchiato, Damiano Scopetti, Nicola Di-Iacovo, Maria Agnese Della-Fazia and Giuseppe Servillo
Int. J. Mol. Sci. 2022, 23(22), 14480; https://doi.org/10.3390/ijms232214480 - 21 Nov 2022
Cited by 2 | Viewed by 2257
Abstract
A cancer outcome is a multifactorial event that comes from both exogenous injuries and an endogenous predisposing background. The healthy state is guaranteed by the fine-tuning of genes controlling cell proliferation, differentiation, and development, whose alteration induces cellular behavioral changes finally leading to [...] Read more.
A cancer outcome is a multifactorial event that comes from both exogenous injuries and an endogenous predisposing background. The healthy state is guaranteed by the fine-tuning of genes controlling cell proliferation, differentiation, and development, whose alteration induces cellular behavioral changes finally leading to cancer. The function of proteins in cells and tissues is controlled at both the transcriptional and translational level, and the mechanism allowing them to carry out their functions is not only a matter of level. A major challenge to the cell is to guarantee that proteins are made, folded, assembled and delivered to function properly, like and even more than other proteins when referring to oncogenes and onco-suppressors products. Over genetic, epigenetic, transcriptional, and translational control, protein synthesis depends on additional steps of regulation. Post-translational modifications are reversible and dynamic processes that allow the cell to rapidly modulate protein amounts and function. Among them, ubiquitination and ubiquitin-like modifications modulate the stability and control the activity of most of the proteins that manage cell cycle, immune responses, apoptosis, and senescence. The crosstalk between ubiquitination and ubiquitin-like modifications and post-translational modifications is a keystone to quickly update the activation state of many proteins responsible for the orchestration of cell metabolism. In this light, the correct activity of post-translational machinery is essential to prevent the development of cancer. Here we summarize the main post-translational modifications engaged in controlling the activity of the principal oncogenes and tumor suppressors genes involved in the development of most human cancers. Full article
(This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Molecules in Cancer)
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Figure 1

37 pages, 2662 KiB  
Review
Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling
by Anmol Sharma, Heena Khan, Thakur Gurjeet Singh, Amarjot Kaur Grewal, Agnieszka Najda, Małgorzata Kawecka-Radomska, Mohamed Kamel, Ahmed E. Altyar and Mohamed M. Abdel-Daim
Int. J. Mol. Sci. 2021, 22(21), 11971; https://doi.org/10.3390/ijms222111971 - 4 Nov 2021
Cited by 46 | Viewed by 5364
Abstract
The ubiquitin-proteasome pathway (UPP) is involved in regulating several biological functions, including cell cycle control, apoptosis, DNA damage response, and apoptosis. It is widely known for its role in degrading abnormal protein substrates and maintaining physiological body functions via ubiquitinating enzymes (E1, E2, [...] Read more.
The ubiquitin-proteasome pathway (UPP) is involved in regulating several biological functions, including cell cycle control, apoptosis, DNA damage response, and apoptosis. It is widely known for its role in degrading abnormal protein substrates and maintaining physiological body functions via ubiquitinating enzymes (E1, E2, E3) and the proteasome. Therefore, aberrant expression in these enzymes results in an altered biological process, including transduction signaling for cell death and survival, resulting in cancer. In this review, an overview of profuse enzymes involved as a pro-oncogenic or progressive growth factor in tumors with their downstream signaling pathways has been discussed. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on modulation of ubiquitin-proteasome pathways in oncogenic signaling. Various in vitro, in vivo studies demonstrating the involvement of ubiquitin-proteasome systems in varied types of cancers and the downstream signaling pathways involved are also discussed in the current review. Several inhibitors of E1, E2, E3, deubiquitinase enzymes and proteasome have been applied for treating cancer. Some of these drugs have exhibited successful outcomes in in vivo studies on different cancer types, so clinical trials are going on for these inhibitors. This review mainly focuses on certain ubiquitin-proteasome enzymes involved in developing cancers and certain enzymes that can be targeted to treat cancer. Full article
(This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Molecules in Cancer)
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