| Grant number: | 11/10321-3 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | September 01, 2011 |
| Effective date (End): | January 31, 2016 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Deborah Schechtman |
| Grantee: | Darlene Aparecida Pena |
| Home Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated scholarship(s): | 14/16037-3 - Conformational antibodies for cPKCs and their applications, BE.EP.DR |
Abstract Embryonic stem cells (ESC) proliferate while retaining the ability to differentiate into several cell types (self-renewal). For the efficient use of ESCs in cell therapy it is necessary to know the specific molecular processes of differentiation and self-renewal of ESC. The family of serine / threonine kinase protein kinase C (PKC) has been identified as key enzymes for the processes of proliferation and differentiation of ES cells. However, the exact function of each isoform, of this family consists of 10 isozymes, is still unclear. In recent years, our laboratory has characterized the role of different isozymes of PKCs in undifferentiated ESC. Our data suggest that among the PKCs expressed in CTE, lower molecular weight forms of PKC²I are expressed in the nucleus of murine ESC and possibly since they not contain the pseudo-substrate responsible for self-inhibition of the enzyme are catalytically active forms of PKC²I. Furthermore, phosphoproteomics studies indicate that most substrates PKC²I in ESC are undifferentiated nuclear proteins that regulate transcription of proteins involved in proliferation/ differentiation. We also noted that during differentiation there is a change of sub-cellular localization of PKC²I expressed in the cytoplasm of various differentiated cells, and abcent in other differentiated cells. Together, these data suggest that PKC²I may be involved in important processes of undifferentiated ESC, such as the maintenance of their undifferentiated state. Thus, this project aims to study the function of PKC²I to this end we will use new strategies such as the development of conformational antibodies specific for active and will identify proteins specifically to active PKCbI. This study will be fundamental to elucidate the signaling cascades that lead to CTE selfI-renewal. As the self-renewal is one of the key processes in carcinogenesis, these results may be later applied to the study of signaling pathways in cancer models. Identifying binding proteins one may specifically regulate protein/ protein interactions which is relevant to the development of new strategies for cell therapy with ESC as well as for the treatment of cancer. | |