Study of the role of STI1 and assotiated factors in the proteostasis network and pluripotency regulation

• Grant number: 19/14741-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): January 01, 2020
• Effective date (End): February 29, 2024
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Camila Felix de Lima Fernandes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 21/13114-0 - Proteostasis as a post-transcriptional mechanism of pluripotency maintenance: the role of STI1 in human induced pluripotent stem cells, BE.EP.DD

Abstract

Stress Inducible Protein 1 (STI1) corresponds to an evolutionary conserved protein, formed by three repetitive tetratricopeptides domains, and two additional domains rich in aspartate and proline. The structure of STI1 is closely associated with its multifunctionality in cells, being found in the cytoplasm, nucleus and extracellular environment. One of the main functions of STI1 is its role as a cochaperone, allowing the formation of a protein complex between HSP70-HSP90 heat shock proteins, aiding in the folding and processing of several other proteins, client of this molecular machinery. The complex formed by STI1 is essential for the maintenance of protein homeostasis (proteostase). Total depletion of STI1 in mice leads to embryo unviability, but despite the elucidated phenotype, the exact molecular mechanisms leading to the early degeneration of these animals are not fully known. Mouse Embryonic Stem Cells (mESCs) represent one of the most efficient in vitro models to mimic the early embryonic development of mammals. ESCs are classified as Pluripotent Stem Cells (PSCs), as they have the ability to differentiate into any adult somatic phenotype under proper stimuli, and can self-renew indefinitely without cellular senescence. PSCs have advanced proteome control mechanisms, including increased synthesis of chaperones and cochaperones, such as STI1. Many crucial factors in the biology of PSCs remain unknown, and therefore understanding the molecular basis associated with the maintenance of pluripotency is of fundamental importance, both for the use of these cells in research of degenerative diseases and aging, as well as the release of their therapeutic potential. Therefore, the present project aims to shed light on aspects associated with the control of PSCs and their potential for differentiation, proliferation and self-renewal through proteostasis mechanisms. Also, we seek to find new molecular pathways, possibly modulated by STI1, associated to the control of pluripotency and initial development of mammals. (AU)

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)

ALVES, RODRIGO NUNES; IGLESIA, REBECA PIATNICZKA; PRADO, MARIANA BRANDAO; MELO ESCOBAR, MARIA ISABEL; BOCCACINO, JACQUELINE MARCIA; FERNANDES, CAMILA FELIX DE LIMA; COELHO, BARBARA PARANHOS; FORTES, AILINE CIBELE; LOPES, MARILENE HOHMUTH. A New Take on Prion Protein Dynamics in Cellular Trafficking. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 20, OCT 2020. (20/07450-5, 17/26158-0, 19/14952-0, 19/11097-1, 20/04687-4, 18/15557-4, 19/12710-9, 19/14741-9)

COELHO, BARBARA PARANHOS; DE LIMA FERNANDES, CAMILA FELIX; BOCCACINO, JACQUELINE MARCIA; DA SILVA SOUZA, MARIA CLARA; MELO-ESCOBAR, MARIA ISABEL; ALVES, RODRIGO NUNES; PRADO, MARIANA BRANDAO; IGLESIA, REBECA PIATNICZKA; CANGIANO, GIOVANNI; MAZZARO, GIULIA LA ROCCA; et al. Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma. FRONTIERS IN ONCOLOGY, v. 10, NOV 12 2020. (19/14552-1, 19/14952-0, 17/26158-0, 20/04687-4, 19/06971-4, 19/11097-1, 19/12710-9, 20/07450-5, 18/15557-4, 19/14741-9)