Molecular mechanisms of functional interaction between Ras and cyclin D1 in Ras-driven malignant cells

• Grant number: 12/20186-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2013
• Effective date (End): May 01, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Hugo Aguirre Armelin
• Grantee: Matheus Henrique dos Santos Dias
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID
• Associated scholarship(s): 16/17945-6 - Proteome/phosphoproteome networks investigation of the complementary role of Cyclin D1 for Ras-driven malignant transformation, BE.EP.PD

Abstract

K-Ras, H-Ras e N-Ras are part of a family of small GTPases which work as "molecular switches" converting the activation of membrane receptors into activation of intracellular signaling pathways such as the MAPK pathway. Gain-of-function mutations in Ras proteins are found in about to 20% of all human tumors, frequently leading to bad prognosis. Among other proteins whose activity has been shown necessary for Ras-driven tumorigenesis, we and others have shown that cyclin D1 is important for the onset and maintenance of Ras-driven malignant phenotypes. Canonically, cyclin D1 is responsible for coupling mitogenic signaling to cell cycle control machinery, through binding to and activating CDKs 4 and 6, controlling the first steps of cell cycle progression. However, novel and CDK 4/6-independent functions unrelated to cell cycle control have been described to this protein. We propose that in Ras-driven malignant cells there is a functional interaction between ciclin D1 and this oncogene; where the function of cyclin D1 is to guarantee cell survival overcoming the Ras oncogenic stress. Confirmation, as well as elucidation of the molecular mechanisms underlying this putative functional interaction between Ras and cyclin D1 are the central goals of this project. (AU)

Scientific publications

(4)

(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)

DIAS, MATHEUS H.; FONSECA, CECILIA S.; ZEIDLER, JULIANNA D.; ALBUQUERQUE, LAYRA L.; DA SILVA, MARCELO S.; CARARO-LOPES, EDUARDO; REIS, MARCELO S.; NOEL, VINCENT; DOS SANTOS, EDMILSON O.; PRIOR, IAN A.; et al. Fibroblast Growth Factor 2 lethally sensitizes cancer cells to stress-targeted therapeutic inhibitors. MOLECULAR ONCOLOGY, v. 13, n. 2, p. 290-306, FEB 2019. (12/20186-9, 13/09040-5, 13/24212-7, 16/17945-6)

ZEIDLER, JULIANNA D.; FERNANDES-SIQUEIRA, LORENA O.; CARVALHO, ANA S.; CARARO-LOPES, EDUARDO; DIAS, MATHEUS H.; KETZER, LUISA A.; GALINA, ANTONIO; DA POIAN, ANDREA T.. Short-term starvation is a strategy to unravel the cellular capacity of oxidizing specific exogenous/endogenous substrates in mitochondria. Journal of Biological Chemistry, v. 292, n. 34, p. 14176-14187, AUG 25 2017. (12/20186-9)

DIAS, MATHEUS H.; KITANO, EDUARDO S.; ZELANIS, ANDRE; IWAI, LEO K.. Proteomics and drug discovery in cancer. DRUG DISCOVERY TODAY, v. 21, n. 2, p. 264-277, FEB 2016. (12/20186-9, 11/11308-0, 14/06579-3, 13/07467-1)

DIAS, MATHEUS H.; FONSECA, CECILIA S.; ZEIDLER, JULIANNA D.; ALBUQUERQUE, LAYRA L.; DA SILVA, MARCELO S.; CARARO-LOPES, EDUARDO; REIS, MARCELO S.; NOEL, VINCENT; DOS SANTOS, EDMILSON O.; PRIOR, IAN A.; et al. Fibroblast Growth Factor 2 lethally sensitizes cancer cells to stress-targeted therapeutic inhibitors. MOLECULAR ONCOLOGY, v. 13, n. 2, p. 17-pg., 2019-02-01. (16/17945-6, 13/09040-5, 12/20186-9, 13/24212-7)