Abstract
The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin–proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as Fbw7) is often mutated in human cancers and functions as a tumor suppressive E3 ligase targeting oncogenic proteins for degradation. SKP2 is a potential drug target for cancer therapy and FBXW7 is useful in determining patient diagnosis, prognosis, and drug sensitivity. In this review, we also discuss other F-box proteins involved in cancer-associated cellular processes such as cell cycle control, epigenetic regulation, epithelial mesenchymal transition, apoptosis/survival, drug resistance, and DNA-damage responses.
Keywords: β-TrCP, E3 ligase, F-box protein, FBXW7, human cancer, proteasome, SCF complex, SKP2, ubiquitin.
Current Cancer Drug Targets
Title:The SCF-type E3 Ubiquitin Ligases as Cancer Targets
Volume: 16 Issue: 2
Author(s): Kyoko Kitagawa and Masatoshi Kitagawa
Affiliation:
Keywords: β-TrCP, E3 ligase, F-box protein, FBXW7, human cancer, proteasome, SCF complex, SKP2, ubiquitin.
Abstract: The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin–proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as Fbw7) is often mutated in human cancers and functions as a tumor suppressive E3 ligase targeting oncogenic proteins for degradation. SKP2 is a potential drug target for cancer therapy and FBXW7 is useful in determining patient diagnosis, prognosis, and drug sensitivity. In this review, we also discuss other F-box proteins involved in cancer-associated cellular processes such as cell cycle control, epigenetic regulation, epithelial mesenchymal transition, apoptosis/survival, drug resistance, and DNA-damage responses.
Export Options
About this article
Cite this article as:
Kitagawa Kyoko and Kitagawa Masatoshi, The SCF-type E3 Ubiquitin Ligases as Cancer Targets, Current Cancer Drug Targets 2016; 16 (2) . https://dx.doi.org/10.2174/1568009616666151112122231
DOI https://dx.doi.org/10.2174/1568009616666151112122231 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
Related Articles
-
p16<sup>INK4</sup> as a Biomarker in Oropharyngeal Squamous Cell Carcinoma
Recent Patents on Biomarkers Clinical Development of 17-Allylamino, 17-Demethoxygeldanamycin
Current Cancer Drug Targets An Update on the Other Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors
Medicinal Chemistry Reviews - Online (Discontinued) Antiproliferative Activity of microRNA-125a and its Molecular Targets
MicroRNA Recent Advances in the Therapeutic Perspectives of Nutlin-3
Current Pharmaceutical Design Microarray Profiling Analysis Uncovers Common Molecular Mechanisms of Rubella Virus, Human Cytomegalovirus, and Herpes Simplex Virus Type 2 Infections in ECV304 Cells
Current Molecular Medicine Antiviral Drugs that Target Cellular Proteins May Play Major Roles in Combating HIV Resistance
Current Pharmaceutical Design Emergence of Functionalized Nanomedicines in Cancer Chemotherapy: Recent Advancements, Current Challenges and Toxicity Considerations
Recent Patents on Nanomedicine Seeing Genes at Work in the Living Brain with Non-Invasive Molecular Imaging
Current Gene Therapy Gene Therapy for Ischemic Brain Diseases
Current Gene Therapy High Mobility Group Box 1 Protein as a Potential Drug Target for Infection- and Injury-Elicited Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Current Chemical Biology Roles of Apoptosis and Cellular Senescence in Cancer and Aging
Current Drug Targets SENP1 as A Biomarker for the Diagnosis of Cancer: Review of the Science and Published Patents
Recent Patents on Biomarkers Blockade of Insulin-Like Growth Factor Type-1 Receptor with Cixutumumab (IMC-A12): A Novel Approach to Treatment for Multiple Cancers
Current Drug Targets Subject Index To Volume 7
Current Drug Targets Cell Cycle Checkpoint Genes and Aneuploidy: A Short Review
Current Genomics The Many Faces of MTA3 Protein in Normal Development and Cancers
Current Protein & Peptide Science ING Proteins in Cellular Senescence
Current Drug Targets Developmental and Biological Insights Obtained from Gene Expression Profiling of the Nematode Caenorhabditis Elegans
Current Genomics