Abstract
The proteasomal pathway of protein degradation involves two discrete steps: ubiquitination and degradation. Blocking protein degradation by inhibiting the proteasome has well described biologic effects and proteasome inhibitors are approved for the treatment of multiple myeloma and mantle cell lymphoma. In contrast, the biological effects and potential therapeutic utility of inhibiting the ubiquitination cascade and the initiating enzyme UBA1 are less well understood. UBA1 is the initial enzyme in the ubiquitination cascade and initiates the transfer of ubiquitin molecules to target proteins where they are degraded by the proteasome. Here, we review the biological effects of UBA1 inhibition and discuss UBA1 inhibitors as potential anti-cancer agents. Similar to proteasome inhibition, blocking UBA1 elicits an unfolded protein response and induces cell death in malignant cells over normal cells. Chemical UBA1 inhibitors have been developed that target different regions of the enzyme and inhibit its function through different mechanisms. These molecules are useful tools to understand the biology of UBA1 and highlight the potential of inhibiting this target for the treatment of malignancy.
Keywords: Ubiquitin, proteasome, UBA1.
Current Pharmaceutical Design
Title:Targeting the Ubiquitin E1 as a Novel Anti-Cancer Strategy
Volume: 19 Issue: 18
Author(s): Wei Xu, Julie L. Lukkarila, Sara R. da Silva, Stacey-Lynn Paiva, Patrick T. Gunning and Aaron D. Schimmer
Affiliation:
Keywords: Ubiquitin, proteasome, UBA1.
Abstract: The proteasomal pathway of protein degradation involves two discrete steps: ubiquitination and degradation. Blocking protein degradation by inhibiting the proteasome has well described biologic effects and proteasome inhibitors are approved for the treatment of multiple myeloma and mantle cell lymphoma. In contrast, the biological effects and potential therapeutic utility of inhibiting the ubiquitination cascade and the initiating enzyme UBA1 are less well understood. UBA1 is the initial enzyme in the ubiquitination cascade and initiates the transfer of ubiquitin molecules to target proteins where they are degraded by the proteasome. Here, we review the biological effects of UBA1 inhibition and discuss UBA1 inhibitors as potential anti-cancer agents. Similar to proteasome inhibition, blocking UBA1 elicits an unfolded protein response and induces cell death in malignant cells over normal cells. Chemical UBA1 inhibitors have been developed that target different regions of the enzyme and inhibit its function through different mechanisms. These molecules are useful tools to understand the biology of UBA1 and highlight the potential of inhibiting this target for the treatment of malignancy.
Export Options
About this article
Cite this article as:
Xu Wei, Lukkarila Julie L., da Silva Sara R., Paiva Stacey-Lynn, Gunning Patrick T. and Schimmer Aaron D., Targeting the Ubiquitin E1 as a Novel Anti-Cancer Strategy, Current Pharmaceutical Design 2013; 19 (18) . https://dx.doi.org/10.2174/1381612811319180004
DOI https://dx.doi.org/10.2174/1381612811319180004 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Identifying Biomarkers of Lung Cancer in the Post-Genomic Era
Current Pharmacogenomics Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME
Anti-Cancer Agents in Medicinal Chemistry Role of the Akt Pathway in Prostate Cancer
Current Cancer Drug Targets Microemulsions and Nanoemulsions for Targeted Drug Delivery to the Brain
Current Nanoscience Sphingolipid Metabolism and Leukemia: A Potential for Novel Therapeutic Approaches
Anti-Cancer Agents in Medicinal Chemistry Onconeural Versus Paraneoplastic Antigens?
Current Medicinal Chemistry Molecular Dynamics Simulations of Protein Targets Identified in Mycobacterium tuberculosis
Current Medicinal Chemistry Methodological Aspects and Applications of In Vivo Imaging of Apoptosis in Oncology: An Illustrative Review
Current Medical Imaging Therapeutic Exploitation of Apoptosis and Autophagy for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Immunogenic Issues Concerning Recombinant Adeno-Associated Virus Vectors for Gene Therapy
Current Gene Therapy CAR T-cell Therapy: A New Era in Cancer Immunotherapy
Current Pharmaceutical Biotechnology Small Molecular Weight Inhibitors of Stress-Activated and Mitogen- Activated Protein Kinases
Mini-Reviews in Medicinal Chemistry Predicating Candidate Cancer-Associated Genes in the Human Signaling Network Using Centrality
Current Bioinformatics Protease Inhibitors with Antileishmanial Activity
Current Enzyme Inhibition Vincristine-Induced Seizure Potentiated by Itraconazole Following RCHOP Chemotherapy for Diffuse Large B-Cell Lymphoma
Current Drug Safety Effects of Epirubicin and Cisplatin Against 4T1 Breast Cancer Cells are Enhanced by Myrtucommulone-A
Anti-Cancer Agents in Medicinal Chemistry An Evolving Role of Piperazine Moieties in Drug Design and Discovery
Mini-Reviews in Medicinal Chemistry Zebrafish as a Model for the Study of the Phase II Cytosolic Sulfotransferases
Current Drug Metabolism Histamine and Histamine Receptor Antagonists in Cancer Biology
Inflammation & Allergy - Drug Targets (Discontinued) Antitumor Pharmacology - Quo Vadis ?
Current Medicinal Chemistry - Anti-Cancer Agents