Abstract
The androgen receptor (AR) plays a critical role in proliferation and viability of prostate cancer cells. Therefore, suppressing AR activity by androgen deprivation or anti-androgen treatment has been the frontline therapy for over six decades. However, these treatment strategies are not curative and patients succumb to castration-resistant disease. Although AR is evidently critical for proliferation of prostate cancer cells, very little is known about its mechanism of action in this process. Over the years, the role of AR in prostate cancer cell proliferation and viability has been studied by focusing primarily on its role as a transcription factor. However, recent observations indicate that besides its role as a transcription factor, AR interacts physically with components of the pre-replication complex (pre-RC) and DNA replication machinery (replitase). These interactions may enable AR to exert control over the process of DNA synthesis. In addition, alterations in the proteins that interact with AR in complexes required for DNA synthesis could lead to the development of hormone-refractory prostate cancer. These observations suggest a paradigm shift for the role of AR in proliferation of prostate cancer cells from its role as a transcription factor to a non-transcriptional role as a component of the replication machinery, interacting with cell cycle regulatory proteins and enzymes of DNA synthesis. We propose that a detailed understanding of the structural interactions between AR and the components of pre-RC and replitase may lead to the development of new strategies for the treatment of prostate cancer.
Keywords: Androgen Receptor, Cell Cycle, Pre-Replication Complex, DNA Replication, Prostate Cancer
Current Protein & Peptide Science
Title: Role of Androgen Receptor in Prostate Cancer Cell Cycle Regulation: Interaction with Cell Cycle Regulatory Proteins and Enzymes of DNA Synthesis
Volume: 11 Issue: 6
Author(s): Arun Sivanandam, Shalini Murthy, Sahn-Ho Kim, Evelyn R. Barrack and G. Prem Veer Reddy
Affiliation:
Keywords: Androgen Receptor, Cell Cycle, Pre-Replication Complex, DNA Replication, Prostate Cancer
Abstract: The androgen receptor (AR) plays a critical role in proliferation and viability of prostate cancer cells. Therefore, suppressing AR activity by androgen deprivation or anti-androgen treatment has been the frontline therapy for over six decades. However, these treatment strategies are not curative and patients succumb to castration-resistant disease. Although AR is evidently critical for proliferation of prostate cancer cells, very little is known about its mechanism of action in this process. Over the years, the role of AR in prostate cancer cell proliferation and viability has been studied by focusing primarily on its role as a transcription factor. However, recent observations indicate that besides its role as a transcription factor, AR interacts physically with components of the pre-replication complex (pre-RC) and DNA replication machinery (replitase). These interactions may enable AR to exert control over the process of DNA synthesis. In addition, alterations in the proteins that interact with AR in complexes required for DNA synthesis could lead to the development of hormone-refractory prostate cancer. These observations suggest a paradigm shift for the role of AR in proliferation of prostate cancer cells from its role as a transcription factor to a non-transcriptional role as a component of the replication machinery, interacting with cell cycle regulatory proteins and enzymes of DNA synthesis. We propose that a detailed understanding of the structural interactions between AR and the components of pre-RC and replitase may lead to the development of new strategies for the treatment of prostate cancer.
Export Options
About this article
Cite this article as:
Sivanandam Arun, Murthy Shalini, Kim Sahn-Ho, R. Barrack Evelyn and Prem Veer Reddy G., Role of Androgen Receptor in Prostate Cancer Cell Cycle Regulation: Interaction with Cell Cycle Regulatory Proteins and Enzymes of DNA Synthesis, Current Protein & Peptide Science 2010; 11 (6) . https://dx.doi.org/10.2174/138920310791824075
DOI https://dx.doi.org/10.2174/138920310791824075 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
-
Targeted Therapy of the Insulin-Like Growth Factor-1 Receptor in Cancer
Combinatorial Chemistry & High Throughput Screening Metformin - The Drug for the Treatment of Autoimmune Diseases; A New Use of a Known Anti-Diabetic Drug
Current Topics in Medicinal Chemistry Future Directions in the Treatment of Neuropathic Pain: A Review on Various Therapeutic Targets
CNS & Neurological Disorders - Drug Targets Soy Isoflavones and Exercise: Possible Benefits for Postmenopausal Womens Cardiovascular Health
Current Women`s Health Reviews Clinical Importance of Assessment of Type 2 Diabetes Mellitus with Visceral Obesity. A Japanese Perspective
Current Diabetes Reviews Genomic and Proteomic Techniques and their Application in Selenium Research
Current Pharmacogenomics Novel and Emerging Targeted Therapies of Colorectal Cancer
Current Clinical Pharmacology Nano-Phytosome: A Developing Platform for Herbal Anti-Cancer Agents in Cancer Therapy
Current Drug Targets Recent Advances in the Chemistry of Phthalimide Analogues and their Therapeutic Potential
Mini-Reviews in Medicinal Chemistry The Advancement of Human Serum Albumin-Based Molecular Probes for Molecular Imaging
Current Pharmaceutical Design Transcription, DNA Damage and Beyond: The Roles of Histone Ubiquitination and Deubiquitination
Current Protein & Peptide Science Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect
Current Drug Targets Detection of Cancer Cells on a Chip
Current Topics in Medicinal Chemistry SELDI Protein Chip Technology for the Detection of Serum Biomarkers for Liver Disease
Protein & Peptide Letters Biochemical Markers for Brain Injury Monitoring in Children with or without Congenital Heart Diseases
CNS & Neurological Disorders - Drug Targets Recent Patents on Light Based Therapies: Photodynamic Therapy, Photothermal Therapy and Photoimmunotherapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Integrins as A New Target for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19
Current Medicinal Chemistry Protein Kinase C Isozymes as Potential Targets for Anticancer Therapy
Current Cancer Drug Targets Reactivation of latent HIV-1 in latently infected cells by coumarin compounds: Hymecromone and ScoparoneReactivation of Latent HIV-1 in Latently Infected Cells by Coumarin Compounds: Hymecromone and Scoparone
Current HIV Research