Life Sciences & Biotechnology
Title : | Investigating CREB as a therapeutic target for cancers by reactivating the epigenetically silenced tumor suppressors |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Prof. sudhakar Baluchamy, Pondicherry University, Puducherry |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | baluchamy@yahoo.com |
Equipments : | sorvall Refrigerated Centrifuge
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Details
Executive Summary : | The regulation of transcriptional activation and repression of both positive and negative regulators is crucial for normal cell proliferation. Dysregulation in these mechanisms can lead to tumorigenesis. Cyclic AMP response element binding (CREB) transcription factor (TF) promotes the transcription of genes involved in cell growth, differentiation, and survival. CREB mediated signaling pathway is hyper-activated in almost all cancer types. CREB transcriptional activation interacts with epigenetic activators, such as p300/CBP via its binding motif CRE. Recent studies have indicated that CREB downregulates some target genes by interacting with co-repressor HDAC and YY1. However, the CREB mediated negative regulation of other targets, including tumor suppressor genes (TsGs) at promoter level through major epigenetic repressors such as DNMT3B, EZH2, and CUL4B, is not yet understood. Tumor suppressor genes (TsGs) normally prevent or suppress cancer development by regulating cell growth, division, and death. Dysregulation of TsGs expression can lead to uncontrolled cell growth and the formation of tumors. PTEN, a well-studied TsG, negatively regulates CREB by dephosphorylating the active form of pCREB through its phosphatase activity. Preliminary data indicated that CREB overexpression down-regulates TsGs, PTEN, and p16, supporting this hypothesis. The combinatorial regulatory effect of CREB, epigenetic repressors, and TsGs in cancers has not been explored. This study focuses on investigating the molecular link between CREB, epigenetic repressors, and TsGs and their regulatory role in normal and cancer cells. Understanding these mechanisms will deepen our knowledge on the contribution of CREB mediated transcriptional networks in carcinogenesis and help devise strategies to reactivate TsGs by inhibiting CREB and epigenetic repressors. |
Co-PI: | Dr. Maheswaran Mani, Pondicherry University, Puducherry-605014 |
Total Budget (INR): | 49,95,870 |
Organizations involved