Specific conformational antibodies for PKC beta I and their applications

• Grant number: 12/24154-4
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2013
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Deborah Schechtman
• Grantee: Deborah Schechtman
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In the last years our lab has been characterizing the role of Protein kinase C (PKC) in undifferentiated murine embryonic stem cells (ESC). Our results suggest that most of the PKC²I substrates in undifferentiated ESC are nuclear proteins involved in the regulation of transcription of proteins involved in proliferaation/ diferentiation. Recent studies also have reported nuclear PKC²I in breast and prostate tumors. These studies determined that PKC²I regulates the phosphorylation of Histone H3 and its methilation in these cells, controling the expression of genes involved in tumor cell proliferation. Together these results contribute to the idea that PKC²I is involved proliferation and self-renewal of ESC and mamary and prostate tumor cells. Therefore, the serine/ threonine kinase , PKC²I can be important for the self-renewal of ESC as well as a key target for therapeutic strategies and prognosis of mamary and prostate tumor. The mechanisms responsible for the nuclear translocation of PKC²I as well as interaction partners of PKC²I in these models are still unknown. Besides that at the present moment few PKC²I substrates have been identified and characterized. We beleive that elucidating the function of PKC²I in ESC as well as in mamary and prostate tumor cells can help us understand the process of self-renewal in these cells. Besides that these studies may aid in the development of new rationaly designed therapeutics that have PKC²I as a target. To this end it is necessary to develop new tools to study the structure of PKC²I as well as to characteize the binding partners of this protein. To this end in the following project we aim to develop conformational antibodies that can be used to chatacterize PKC²I structurally and functionaly in undifferentiated ESC, and mamary and prostate tumor cells. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE OLIVEIRA, PAULO SERGIO L.; FERRAZ, FELIPE AUGUSTO N.; PENA, DARLENE A.; PRAMIO, DIMITRIUS T.; MORAIS, FELIPE A.; SCHECHTMAN, DEBORAH. Revisiting protein kinase-substrate interactions: Toward therapeutic development. Science Signaling, v. 9, n. 420, MAR 22 2016. (12/24154-4, 15/17812-3, 11/10321-3, 15/21786-8)

DUARTE, MARIANA LEMOS; PENA, DARLENE APARECIDA; NUNES FERRAZ, FELIPE AUGUSTO; BERTI, DENISE APARECIDA; PASCHOAL SOBREIRA, TIAGO JOSE; COSTA-JUNIOR, HELIO MIRANDA; ABDEL BAQUI, MUNIRA MUHAMMAD; DISATNIK, MARIE-HELENE; XAVIER-NETO, JOSE; LOPES DE OLIVEIRA, PAULO SERGIO; et al. Protein folding creates structure-based, noncontiguous consensus phosphorylation motifs recognized by kinases. SCIENCE SIGNALING, v. 7, n. 350, p. 8-pg., 2014-11-04. (11/10321-3, 12/24154-4, 10/18640-8, 10/15424-2)

DUARTE, MARIANA LEMOS; PENA, DARLENE APARECIDA; NUNES FERRAZ, FELIPE AUGUSTO; BERTI, DENISE APARECIDA; PASCHOAL SOBREIRA, TIAGO JOSE; COSTA-JUNIOR, HELIO MIRANDA; ABDEL BAQUI, MUNIRA MUHAMMAD; DISATNIK, MARIE-HELENE; XAVIER-NETO, JOSE; LOPES DE OLIVEIRA, PAULO SERGIO; et al. Protein folding creates structure-based, noncontiguous consensus phosphorylation motifs recognized by kinases. Science Signaling, v. 7, n. 350, NOV 4 2014. (10/15424-2, 11/10321-3, 10/18640-8, 12/24154-4)

PENA, DARLENE APARECIDA; DE ANDRADE, VICTOR PIANA; FERNANDES SILVA, GABRIELA AVILA; NEVES, JOSE IVANILDO; LOPES DE OLIVEIRA, PAULO SERGIO; MANSO ALVES, MARIA JULIA; DEVI, LAKSHMI A.; SCHECHTMAN, DEBORAH. Rational design and validation of an anti-protein kinase C active-state specific antibody based on conformational changes. SCIENTIFIC REPORTS, v. 6, FEB 25 2016. (11/10321-3, 12/24154-4, 12/17279-5)

DE OLIVEIRA, PAULO SERGIO L.; FERRAZ, FELIPE AUGUSTO N.; PENA, DARLENE A.; PRAMIO, DIMITRIUS T.; MORAIS, FELIPE A.; SCHECHTMAN, DEBORAH. Revisiting protein kinase-substrate interactions: Toward therapeutic development. SCIENCE SIGNALING, v. 9, n. 420, p. 12-pg., 2016-03-22. (15/21786-8, 15/17812-3, 11/10321-3, 12/24154-4)