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
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...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
-
Immunotherapy with Tumor Vaccines for the Treatment of Malignant Gliomas
Current Drug Discovery Technologies Targeting Apoptosis Pathways in Cancer Therapy
Current Cancer Drug Targets Pharmaceutical Perspectives of HECT-TYPE Ubiquitin Ligase Smurf1
Current Pharmaceutical Design Lopinavir Loaded Spray Dried Liposomes with Penetration Enhancers for Cytotoxic Activity
Infectious Disorders - Drug Targets Astragalin Attenuates UVB Radiation-induced Actinic Keratosis Formation
Anti-Cancer Agents in Medicinal Chemistry Curcumin Targets in Inflammation and Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate
Current Drug Delivery Mathematical Modeling of the Cancer Cell ’ s Control Circuitry: Paving the Way to Individualized Therapeutic Strategies
Current Signal Transduction Therapy Radionuclide Liver Cancer Therapies: From Concept to Current Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Vitamin D Analogs- Drug Design Based on Proteins Involved in Vitamin D Signal Transduction
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Inhibition of Autophagy by Targeting ATG4B: Promises and Challenges of An Emerging Anti-cancer Strategy
Clinical Cancer Drugs Cell Responses to Oxidative Stressors
Current Pharmaceutical Design The Use of SIFT-MS in Profiling the Faecal Volatile Metabolome in Horses with Colic: A Pilot Study
Current Analytical Chemistry Systemic Redox Biomarkers in Neurodegenerative Diseases
Current Drug Metabolism Ginger and Heart Health: From Mechanisms to Therapeutics
Current Molecular Pharmacology Susceptibility Risk Alleles of -238G/A, -308G/A and -1031T/C Promoter Polymorphisms of TNF-α Gene to Uterine Leiomyomas
Recent Advances in DNA & Gene Sequences (Discontinued) Natural Product-Derived Spirooxindole Fragments Serve as Privileged Substructures for Discovery of New Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Local Melatonin Regulates Inflammation Resolution: A Common Factor in Neurodegenerative, Psychiatric and Systemic Inflammatory Disorders
CNS & Neurological Disorders - Drug Targets Editorial (Metastases Prevention is the Cure)
Current Cancer Therapy Reviews Vitamin D Deficiency: Universal Risk Factor for Multifactorial Diseases?
Current Drug Targets