Abstract
Over the past decade, the promising results of UPSIs (UPS inhibitors) in eliciting apoptosis in various cancer cells, and the approval of the first UPSI (Bortezomib/Velcade/PS-341) for the treatment of multiple myeloma have raised interest in assessing the death program activated upon proteasomal blockage. Several reports indicate that UPSIs stimulate apoptosis in malignant cells by operating at multiple levels, possibly by inducing different types of cellular stress. Normally cellular stress signals converge on the core elements of the apoptotic machinery to trigger the cellular demise. In addition to eliciting multiple stresses, UPSIs can directly operate on the core elements of the apoptotic machinery to control their abundance. Alterations in the relative levels of anti and pro-apoptotic factors can render cancer cells more prone to die in response to other anti-cancer treatments. Aim of the present review is to discuss those core elements of the apoptotic machinery that are under the control of the UPS.
Keywords: Apoptosis, caspases, IAP, IBM, bortezomib, Bcl-2, mitochondria, death receptors, apoptosome, p53
Current Molecular Pharmacology
Title: Inhibitors of the Ubiquitin-Proteasome System and the Cell Death Machinery: How Many Pathways are Activated?
Volume: 1 Issue: 1
Author(s): Claudio Brancolini
Affiliation:
- Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia, Universita di Udine. P.le Kolbe 4 - 33100 Udine, Italy.,Italy
Keywords: Apoptosis, caspases, IAP, IBM, bortezomib, Bcl-2, mitochondria, death receptors, apoptosome, p53
Abstract: Over the past decade, the promising results of UPSIs (UPS inhibitors) in eliciting apoptosis in various cancer cells, and the approval of the first UPSI (Bortezomib/Velcade/PS-341) for the treatment of multiple myeloma have raised interest in assessing the death program activated upon proteasomal blockage. Several reports indicate that UPSIs stimulate apoptosis in malignant cells by operating at multiple levels, possibly by inducing different types of cellular stress. Normally cellular stress signals converge on the core elements of the apoptotic machinery to trigger the cellular demise. In addition to eliciting multiple stresses, UPSIs can directly operate on the core elements of the apoptotic machinery to control their abundance. Alterations in the relative levels of anti and pro-apoptotic factors can render cancer cells more prone to die in response to other anti-cancer treatments. Aim of the present review is to discuss those core elements of the apoptotic machinery that are under the control of the UPS.
Export Options
About this article
Cite this article as:
Brancolini Claudio, Inhibitors of the Ubiquitin-Proteasome System and the Cell Death Machinery: How Many Pathways are Activated?, Current Molecular Pharmacology 2008; 1(1) . https://dx.doi.org/10.2174/1874467210801010024
DOI https://dx.doi.org/10.2174/1874467210801010024 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |

- Author Guidelines
- Editorial Policies
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Allegations from Whistleblowers
- Publishing Ethics and Rectitude
- Increase Visibility Of Your Article
- Archiving Policies
- Reviewer Guidelines
- Guest Editor Guidelines
- Board Recruitment Workflow
- Short Guide
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Announcements
- Forthcoming Thematic Issues
Related Articles
-
Cationic Liposome Mediated Delivery of FUS1 and hIL-12 Coexpression Plasmid Demonstrates Enhanced Activity against Human Lung Cancer
Current Cancer Drug Targets PEDF as an Emerging Therapeutic Candidate for Osteosarcoma
Current Cancer Drug Targets 3-Hydroxy-2-phenyl-4(1H)-quinolinones as Promising Biologically Active Compounds
Mini-Reviews in Medicinal Chemistry Targeting Tumor Microenvironment with Silibinin: Promise and Potential for a Translational Cancer Chemopreventive Strategy
Current Cancer Drug Targets Prostaglandin E<sub>2</sub> Receptor 4 (EP4): A Promising Therapeutic Target for the Treatment of Cancer and Inflammatory Diseases
Current Chemical Biology Inhibitors of HDACs - Effective Drugs Against Cancer?
Current Cancer Drug Targets Therapeutic Potential of Endothelial Progenitor Cells in the Field of Orthopaedics
Current Stem Cell Research & Therapy Brachytherapy: State of the Art and Possible Improvements
Anti-Cancer Agents in Medicinal Chemistry Structure Based Design, Synthesis, and Evaluation of Potential Inhibitors of Steroid Sulfatase
Current Topics in Medicinal Chemistry Monoclonal Antobodies: Application in Radiopharmacy
Current Radiopharmaceuticals Idronoxil as an Anticancer Agent: Activity and Mechanisms
Current Cancer Drug Targets Pharmacokinetics of Polymeric Micelles for Cancer Treatment
Current Drug Metabolism bHLH Transcription Factors Inhibitors for Cancer Therapy: General Features for In Silico Drug Design
Current Medicinal Chemistry Genesis of Dihydropyrimidinone Calcium Channel Blockers: Recent Progress in Structure-Activity Relationships and Other Effects
Mini-Reviews in Medicinal Chemistry Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review of SIRTUIN Activators as Potential Immunomodulators and their Influences on other Dysfunctions
Endocrine, Metabolic & Immune Disorders - Drug Targets The Fate of Nanoparticles In Vivo and the Strategy of Designing Stealth Nanoparticle for Drug Delivery
Current Drug Targets Attacking c-Myc: Targeted and Combined Therapies for Cancer
Current Pharmaceutical Design Nucleic Acid Carrier Systems Based on Polyethylenimine Conjugates for the Treatment of Metastatic Tumors
Current Medicinal Chemistry Nuciferine Inhibits Skin Cutaneous Melanoma Cell Growth by Suppressing TLR4/NF-κB Signaling
Anti-Cancer Agents in Medicinal Chemistry Current Developments in the Analysis of Proteomic Data: Artificial Neural Network Data Mining Techniques for the Identification of Proteomic Biomarkers Related to Breast Cancer
Current Proteomics