Abstract
Neuronal cell specific cyclin-dependent kinase 5 (Cdk5) is a known regulator of neurodegenerative disorders such as Alzheimers and Parkinsons diseases. We report that Cdk5 also plays an important role in the proliferation of breast cancer cells MCF-7 and MDA MB-231 and is functionally involved in chemosensitivity as well as in cell death pathways induced by anti-cancer drug carboplatin (Carb). Here, we demonstrate that carboplatin induced Cdk5 activation under positive regulation of ERK, promotes cell death in MCF-7 and MDA MB-231 cells. DNA-damage stress enhanced ERK activity utilizes Cdk5 as one of its downstream targets for the execution of death signal in carboplatin induced death in MCF-7 and MDA MB-231 cells. Additionally, present data clearly indicates that activated Cdk5 modulates p53 transactivation in MCF-7 cells. However, in p53 mutant MDA MB-231 cells, Cdk5 mediated cell death is likely to be p53 independent. Collectively, our findings not only draw attention to the extra-neuronal functions of Cdk5 but also propose Cdk5 as a novel and potential therapeutic target of chemotherapeutic drugs.
Keywords: Carboplatin, Cdk5, ERK, p53
Current Cancer Drug Targets
Title: Cell Cycle Regulatory Protein 5 (Cdk5) is a Novel Downstream Target of ERK in Carboplatin Induced Death of Breast Cancer Cells (Supplementary Data)
Volume: 8 Issue: 8
Author(s): Ankur Kumar Upadhyay, Amrendra Kumar Ajay, Sandeep Singh and Manoj Kumar Bhat
Affiliation:
Keywords: Carboplatin, Cdk5, ERK, p53
Abstract: Neuronal cell specific cyclin-dependent kinase 5 (Cdk5) is a known regulator of neurodegenerative disorders such as Alzheimers and Parkinsons diseases. We report that Cdk5 also plays an important role in the proliferation of breast cancer cells MCF-7 and MDA MB-231 and is functionally involved in chemosensitivity as well as in cell death pathways induced by anti-cancer drug carboplatin (Carb). Here, we demonstrate that carboplatin induced Cdk5 activation under positive regulation of ERK, promotes cell death in MCF-7 and MDA MB-231 cells. DNA-damage stress enhanced ERK activity utilizes Cdk5 as one of its downstream targets for the execution of death signal in carboplatin induced death in MCF-7 and MDA MB-231 cells. Additionally, present data clearly indicates that activated Cdk5 modulates p53 transactivation in MCF-7 cells. However, in p53 mutant MDA MB-231 cells, Cdk5 mediated cell death is likely to be p53 independent. Collectively, our findings not only draw attention to the extra-neuronal functions of Cdk5 but also propose Cdk5 as a novel and potential therapeutic target of chemotherapeutic drugs.
Export Options
About this article
Cite this article as:
Upadhyay Kumar Ankur, Ajay Kumar Amrendra, Singh Sandeep and Bhat Kumar Manoj, Cell Cycle Regulatory Protein 5 (Cdk5) is a Novel Downstream Target of ERK in Carboplatin Induced Death of Breast Cancer Cells (Supplementary Data), Current Cancer Drug Targets 2008; 8 (8) . https://dx.doi.org/10.2174/156800908786733405
DOI https://dx.doi.org/10.2174/156800908786733405 |
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
-
Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil
Anti-Cancer Agents in Medicinal Chemistry Inducing Synthetic Lethality using PARP Inhibitors
Current Clinical Pharmacology Rational Identification of Enoxacin as a Novel V-ATPase-Directed Osteoclast Inhibitor
Current Protein & Peptide Science CXCR1/2 Chemokine Network Regulates Melanoma Resistance to Chemotherapies Mediated by NF-κB
Current Molecular Medicine Quantum Noise Removal from Breast Mammograms Using Genetic Programming based Hybrid Ensemble Filter
Current Medical Imaging Musculoskeletal Adverse Drug Reactions: A Review of Literature and Data from ADR Spontaneous Reporting Databases
Current Drug Safety mTOR Targeted Cancer Chemoprevention by Flavonoids
Current Medicinal Chemistry Bioavailability Enhancement Strategies: Basics, Formulation Approaches and Regulatory Considerations
Current Drug Delivery Impact of the Emulsification-Diffusion Method on the Development of Pharmaceutical Nanoparticles
Recent Patents on Drug Delivery & Formulation Augmentation Therapy with Alpha1-antitrypsin: Novel Perspectives
Cardiovascular & Hematological Disorders-Drug Targets Novel Nanotechnology Approaches for Targeted Cancer Therapy
Recent Patents on Nanomedicine Altered Glycosylation of Proteins in Cancer: What Is the Potential for New Anti-Tumour Strategies
Anti-Cancer Agents in Medicinal Chemistry Potential Gene Therapy Strategies for Cancer Stem Cells
Current Gene Therapy Radiolabelled Peptides and Monoclonal Antibodies for Therapy Decision Making in Inflammatory Diseases
Current Pharmaceutical Design Current Management of Chordoma
Current Drug Therapy DMBA- Induced Breast Cancer: A Hormonal Camouflage
Current Cancer Therapy Reviews PET in Anti-Cancer Drug Development and Therapy
Recent Patents on Anti-Cancer Drug Discovery Determination of Epsilon Aminocaproic Acid Based on Charge Transfer Complexation with p-Nitrophenlol by Spectrophotometry
Current Pharmaceutical Analysis Erratum
Current Proteomics Quaternary Structure, Substrate Selectivity and Inhibitor Design for SARS 3C-Like Proteinase
Current Pharmaceutical Design