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
-
Sirtuins Family- Recent Development as a Drug Target for Aging, Metabolism, and Age Related Diseases
Current Drug Targets Resistance to Anti-VEGF Agents
Current Pharmaceutical Design Impact of Oncogenic Protein Tyrosine Phosphatases in Cancer
Anti-Cancer Agents in Medicinal Chemistry Treating Cancer and No-Cancer Pain in Older and Oldest Old Patients
Current Pharmaceutical Design Id-1B, an Alternatively Spliced Isoform of the Inhibitor of Differentiation-1, Impairs Cancer Cell Malignancy Through Inhibition of Proliferation and Angiogenesis
Current Molecular Medicine Cathepsin D as a Promising Target for the Discovery of Novel Anticancer Agents
Current Cancer Drug Targets Statins-Mediated Inhibition of Rho GTPases as a Potential Tool in Anti-Tumor Therapy
Mini-Reviews in Medicinal Chemistry Active Metabolites Resulting from Decarboxylation, Reduction and Ester Hydrolysis of Parent Drugs
Current Drug Metabolism The Relation Between the Chemical Structure of Flavonoids and Their Estrogen-Like Activities
Current Medicinal Chemistry Mangiferin – a Bioactive Xanthonoid, not only from Mango and not just Antioxidant
Mini-Reviews in Medicinal Chemistry Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents
Current Medicinal Chemistry Antigenic Peptide Vaccination: Provoking Immune Response and Clinical Benefit for Cancer
Current Immunology Reviews (Discontinued) Anti-Aging Property of G2013 Molecule as a Novel Immunosuppressive Agent on Enzymatic and Non-Enzymatic Oxidative Stress Determinants in Rat Model
Current Drug Discovery Technologies Delivery Systems for Antimicrobial Peptides and Proteins: Towards Optimization of Bioavailability and Targeting
Current Pharmaceutical Biotechnology Targeting ErbB Receptors in High-Grade Glioma
Current Pharmaceutical Design NSAIDs and Chemoprevention
Current Cancer Drug Targets Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells
Current Cancer Drug Targets Circulating Tumor Cells (CTCs) as a Liquid Biopsy Material and Drug Target
Current Drug Targets The Insulin-like Growth Factor-1 Axis and its Potential as a Therapeutic Target in Central Nervous System (CNS) Disorders
Central Nervous System Agents in Medicinal Chemistry Overactive Bladder - Current Treatment Modalities
Current Women`s Health Reviews