GCN1 and its interactor Yih1/IMPACT: their function in and beyond translational control

• Grant number: 14/23889-6
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: March 02, 2015
• End date: May 21, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Beatriz Amaral de Castilho
• Grantee: Beatriz Amaral de Castilho
• Visiting researcher: Evelyn Sattlegger
• Visiting researcher institution: Massey University, New Zealand
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 09/52047-5 - Translational regulation mediated by elF2 in eukaryotes, AP.TEM

Abstract

Dr. Sattlegger's visit to my group aims at strengthening our research regarding the function of a highly conserved protein named Yih1 in the yeast S. cerevisiae and IMPACT in mammals. Previous works from both Dr. Sattlegger's and my group have shown that Yih1/IMPACT is an inhibitor of the protein kinase, GCN2. GCN2 is activated by amino acid starvation and a variety of other stress conditions, down-regulating general protein synthesis. As a consequence, a program of gene expression is activated that allows cells to recover from the initial stress. IMPACT is highly abundant in neuronal cells, where it hampers this response. Yih1 and IMPACT interact with GCN1, translating ribosomes and actin. During this 2 and 1/2 month visit by Dr. Sattlegger, we will work on interactors of Yih1 and IMPACT, systematizing existing data from both our laboratories, evaluating experimentally the nature of several complexes that IMPACT may participate in neuronal cells. This visit will provide grounds for further complementary studies in our groups aimed at understanding in more depth the mechanism of how this conserved protein regulates GCN2 and at identifying other cellular processes in which Yih1/IMPACT participates. We hope that further advances in the characterization of this protein may elucidate the relevance of IMPACT for neuronal biology. (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)

SILVA, RICHARD C.; SATTLEGGER, EVELYN; CASTILHO, BEATRIZ A.. Perturbations in actin dynamics reconfigure protein complexes that modulate GCN2 activity and promote an eIF2 response. Journal of Cell Science, v. 129, n. 24, p. 4521-4533, DEC 15 2016. (14/17145-4, 14/23889-6, 09/52047-5)

SILVA, RICHARD C.; CASTILHO, BEATRIZ A.; SATTLEGGER, EVELYN. A Rapid Extraction Method for mammalian cell cultures, suitable for quantitative immunoblotting analysis of proteins, including phosphorylated GCN2 and eIF2 alpha. METHODSX, v. 5, p. 75-82, 2018. (14/23889-6, 14/17145-4, 09/52047-5)