Mecanisms of regulation of the expression of the atypical protein kinase C PKMz and identification of interacting proteins in a neuro specific context.

• Grant number: 15/17812-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2015
• Effective date (End): March 28, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Deborah Schechtman
• Grantee: Dimitrius Tansini Pramio
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Breast cancer is a frequent disease in women, and presents a heterogeneous clinical behavior, being composed by an array of molecular profiles. In this context, the protein kinase C family, a group of ten serine/threonine kinases, is of extreme importance, being related with several cellular functions. However, the exact role of each isoform is not fully understood in all the subtypes of this disease. The identification of the differential activity, subcellular localization and substrate characterization of each specific isoform in specific breast cancer subtypes is, therefore, essential for a better understanding of breast cancer biology.Our group recently developed monoclonal and polyclonal antibodies which specifically recognize active classical PKCs (cPKCs), and with this innovative tool in hands we propose to study the cPKCs activity in a breast cancer cell line, MCF7, representative of luminal A positive estrogen receptor subtype. We are also going to utilize this tool in samples from luminal A patients. Previous data from our group showed that PKCsbI and bII are the major nuclear isoforms in MCF7 cells. We are now going to detect the possible nuclear substrates of these enzymes through Bimolecular Fluorescence Complementation method, and also through immunoprecipitation. Still, we are going to observe the phosphorylation in specific sites of histones, which could act as important epigenetic marks, by performing in vitro assays and chromatin immunoprecipitation, validating the data in samples from luminal A patients. This way, we are going to i

Scientific publications

(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)

PRAMIO, DIMITRIUS TANSINI; VIECELI, FELIPE MONTELEONE; VARELLA-BRANCO, ELISA; GOES, CAROLINA PURCELL; KOBAYASHI, GERSON SHIGERU; PELEGRINA, DIOGO VIEIRA DA SILVA; MORAES, BEATRIZ CAROLINE DE; EL ALLAM, AICHA; DE KUMAR, BONY; JARA, GABRIEL; et al. DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKM zeta. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, v. 1866, n. 1, p. 13-pg., 2023-01-25. (19/06982-6, 15/24046-5, 20/13929-1, 20/16204-8, 15/17812-3)

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)