Study of nuclear localization signal (NLS) of Maspin.

• Grant number: 12/18474-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2012
• End date: April 30, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Nathalie Cella
• Grantee: Thiago Sartorato Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Maspin is a protein which has an important role as a tumor suppressor. However, recently evidences suggest that this effect is only observed when this protein is in the nucleus, but not in the cytoplasm. Therefore, subcelular localization is essential to determine if the expression is associated with a good or bad cancer prognosis. Even though protein synthesis occurs in the cytoplasm, many proteins act in the nucleus and there is a mechanism which modulates protein translocation to the nucleus. To this end, these proteins cross the nuclear pore complexes (NPC) have a specific selective potential. Proteins with nuclear roles have nuclear localization signals (NLS) and nuclear transporters, the karyopherins, bind to cross nuclear pores. The NLSs have extremely conserved basic amino acids which are essential for the nuclear import. Hence, mutations in these amino acids can help on the identification of new nuclear localization signals responsible to for nuclear targeting. Thus, with an appropriate prediction algorithm which is based on the protein sequence and on the position of the NLS on the protein tridimensional structure, the aim of this project is to experimentally test the predicted maspin NLS. Therefore, this project can bring new insights into the mechanism which regulates maspin subcellular localization, which could be a new target in cancer therapy.