Abstract
Ubiquitylation is an essential cellular process, and yet many cancer cells appear to be more reliant upon it than normal cells as they are surprisingly sensitive to proteasome inhibitors (PI) and proteasome inhibitor drugs are well tolerated in vivo. Several reviews have suggested that specific protein targets account for PI induced cell death, but fail to adequately explain why cancer cells are more sensitive than normal cells to PIs. We review the evidence for these models, focusing primarily on inducers of cell death including p53 and the pro-apoptotic Bcl-2 Homology proteins (BH3 proteins) and propose an additional hypothesis; that a tumour cells abnormal physiology makes it particularly reliant upon the proteasome. This hypothesis is well supported in the case of Multiple Myelomas, that may produce large amounts of antibodies and are therefore under considerable ER strain and in turn particularly reliant upon the proteasome to clear the large numbers of misfolded proteins. We propose that other cell types, tumor or non tumour, that are already under ER stress, or its equivalent, maybe particularly susceptible to proteasome inhibitors.
Current Cancer Drug Targets
Title: Ubiquitylation and Cancer Development
Volume: 8 Issue: 2
Author(s): John Silke, Maria Miasari and Hamsa Puthalakath
Affiliation:
Abstract: Ubiquitylation is an essential cellular process, and yet many cancer cells appear to be more reliant upon it than normal cells as they are surprisingly sensitive to proteasome inhibitors (PI) and proteasome inhibitor drugs are well tolerated in vivo. Several reviews have suggested that specific protein targets account for PI induced cell death, but fail to adequately explain why cancer cells are more sensitive than normal cells to PIs. We review the evidence for these models, focusing primarily on inducers of cell death including p53 and the pro-apoptotic Bcl-2 Homology proteins (BH3 proteins) and propose an additional hypothesis; that a tumour cells abnormal physiology makes it particularly reliant upon the proteasome. This hypothesis is well supported in the case of Multiple Myelomas, that may produce large amounts of antibodies and are therefore under considerable ER strain and in turn particularly reliant upon the proteasome to clear the large numbers of misfolded proteins. We propose that other cell types, tumor or non tumour, that are already under ER stress, or its equivalent, maybe particularly susceptible to proteasome inhibitors.
Export Options
About this article
Cite this article as:
Silke John, Miasari Maria and Puthalakath Hamsa, Ubiquitylation and Cancer Development, Current Cancer Drug Targets 2008; 8 (2) . https://dx.doi.org/10.2174/156800908783769300
DOI https://dx.doi.org/10.2174/156800908783769300 |
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
-
Combined Chemotherapy or Biotherapy with Jasmonates: Targeting Energy Metabolism for Cancer Treatment
Current Pharmaceutical Biotechnology Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells
Current Alzheimer Research Evolution of Resistance to Cancer Therapy
Current Pharmaceutical Design Nanomedicine: A New Frontier in Cancer Therapeutics
Current Drug Delivery Syntheses of 2,3-Diarylated 2H-Benzo[e][1,2]Thiazine 1,1-Dioxides and their 3,4-Dihydro Derivatives, and Assessment of their Inhibitory Activity Against MCF-7 Breast Cancer Cells
Medicinal Chemistry Hyperglycemia, Hypoglycemia and Dementia: Role of Mitochondria and Uncoupling Proteins
Current Molecular Medicine Psychotropic Medications and the Treatment of Human Prion Diseases
CNS & Neurological Disorders - Drug Targets Resisting the Resistance in Cancer: Cheminformatics Studies on Short- Path Base Excision Repair Pathway Antagonists Using Supervised Learning Approaches
Combinatorial Chemistry & High Throughput Screening Chemistry and Pharmacological Properties of Some Natural and Synthetic Antioxidants for Heavy Metal Toxicity
Current Medicinal Chemistry Pharmacophores for Ligand Recognition and Activation / Inactivation of the Cannabinoid Receptors
Current Pharmaceutical Design Development of PET Probes for Cancer Imaging
Current Topics in Medicinal Chemistry Systems Biology of Apoptosis and Survival: Implications for Drug Development
Current Pharmaceutical Design Genetic Factors in Parkinsons Disease and Potential Therapeutic Targets
Current Neuropharmacology New Approaches to the Modulation of the Cyclooxygenase-2 and 5-Lipoxygenase Pathways
Current Topics in Medicinal Chemistry Antibody-Drug Conjugate Targets
Current Cancer Drug Targets Therapeutic Perspectives of Inhibitors of Endocannabinoid Degradation
Current Drug Targets - CNS & Neurological Disorders Protein Folding and Misfolding, Endoplasmic Reticulum Stress in Neurodegenerative Diseases: in Trace of Novel Drug Targets
Current Protein & Peptide Science In silico Studies Toward the Discovery of Novel Type-II Inhibitors of TrkA: Pharmacophore-based 3D-QSAR Modeling, Database Screening and Molecular Docking
Letters in Drug Design & Discovery Identification and Targeting of Tumor Escape Mechanisms: A New Hope for Cancer Therapy?
Current Pharmaceutical Design Telomere Maintenance Mechanisms in Cancer: Clinical Implications
Current Pharmaceutical Design