Life Sciences & Biotechnology
Title : | Identification & characterization of cis- Regulatory elements of Pras40 promoter and studying protein-protein interaction between PRAS40-mTORC1 to understand PRAS40 regulation in cancer to determine as a potent therapeutic target |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Prof. Ampasala Dinakara Rao, Pondicherry University |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | ampasaladr@bicpu.edu.in |
Equipments : | Real Time PCR |
Details
Executive Summary : | The proline-rich Akt substrate of 40kDa (PRAS40)is a substrate of Akt and a component of the mammalian target of rapamycin complex 1(mTORC1). The biological activity of PRAS40 includes cell growth, apoptosis, autophagy, oxidative stress, and angiogenesis. It is expressed in number of tissues. In literature, cell type and tissue where PRAS40 expressed have been briefly described whereas allied information on the genetic elements that describe the gene’s promoter and regulate specific transcription domains remains unrevealed. PRAS40 take part in the regulation of mTORC1,PRAS40-mTORC1 interaction could inhibit the activity of mTORC1. Phosphorylation of PRAS40 leads to separation of PRAS40 from mTORC1 and removes inhibitory constraint that intervened activation of downstream regulators that control the various regulatory processes like protein synthesis, apoptosis and autophagy. The ability to rapidly increase protein synthesis or deregulation of apoptosis or autophagy are crucial factors for cancerous growth. The Hyper-phosphorylation of PRAS40 have been documented in numerous malignancies including hepatocellular carcinoma, melanoma, prostate cancer, gastric cancer, glioblastoma, non-small cell lung cancer (NSCLC). Over the past few years novel insights have been reported that mTORC1-PRAS40 association as the best oncogenic regulatory target. Defining and characterizing cis-regulatory elements of the human PRAS40 will elucidate the genetic mechanism that regulates human PRAS40expression. Bioinformatics tools and molecular techniques are used in determining cis-regulatory region as well as transcription factors to study the regulation of PRAS40 expression. At the same time, study about Protein-protein interaction between PRAS40-mTORC1 would assist in designing potential inhibitors, which can possibly a drug target in cancer. Several computational approaches are used to model a well defined 3D structures of protein, to study the protein-protein interaction (PPI) between PRAS40-mTORC1 and identifying novel chemical inhibitory molecules by virtual screening approach.The identified chemical molecule(s) will be used to determine its inhibitory effect on PRAS40 and its regulatory role on PRAS40-mTORC1 interaction which are involved in oncogenic pathway by experimental biology approaches. |
Total Budget (INR): | 44,77,264 |
Organizations involved