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Current Cancer Drug Targets
ISSN (Print): 1568-0096
ISSN (Online): 1873-5576
DOI: 10.2174/156800908786733405      Price:  $58

Cell Cycle Regulatory Protein 5 (Cdk5) is a Novel Downstream Target of ERK in Carboplatin Induced Death of Breast Cancer Cells (Supplementary Data)

Author(s): Ankur Kumar Upadhyay, Amrendra Kumar Ajay, Sandeep Singh and Manoj Kumar Bhat
Pages 741-752 (12)
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.
Carboplatin, Cdk5, ERK, p53
National Centre for Cell Science, NCCS Complex, Ganeshkhind, PUNE–411 007, India.