SREBF1 promotes homeostatic control of lipids in response to DNA damage
Start Date
29-4-2022 2:15 PM
Location
Alter Hall Poster Session 1 - 2nd floor
Abstract
Sterol regulatory element-binding protein 1 is a transcription factor encoded by the SREBF1 gene. It functions in cholesterol biosynthesis and lipid homeostasis. Cancer cells are known to utilize lipids as building blocks for rapid proliferation. Therefore, we hypothesized that inhibition of SREBF1 leads to reduced cancer cell growth and progression. We used the Catalogue of Somatic Mutations in Cancer (COSMIC) to identify mutations in SREBF1 across different cancers. Using statistical and bioinformatics tools, we examined how mutation load correlates with tissue type, age, and pathogenicity to reveal the functional consequences of cancer-associated disruptions to SREBF1. Additionally, we used the fission yeast, Schizosaccharomyces pombe, to investigate the effects that disrupting the SREBF1 homolog, Sre1, have on viability, the DNA damage response (DDR), and lipid levels. When subjected to UV damage, cell viability decreases for both wildtype and sre1 mutant strains. However, the effect is more pronounced in the latter, indicating sre1 is required for the response to genotoxic stress. Furthermore, following DNA damage, lipid levels increased in the sre1 mutant relative to wild type cells, suggesting a role for Sre1 in keeping lipid abundance in conditions that favor cancer progression. Altogether, these data imply that regulation of lipid metabolism by Sre1 is important to deploy homeostatic balance in the aftermath of genotoxic insults.
SREBF1 promotes homeostatic control of lipids in response to DNA damage
Alter Hall Poster Session 1 - 2nd floor
Sterol regulatory element-binding protein 1 is a transcription factor encoded by the SREBF1 gene. It functions in cholesterol biosynthesis and lipid homeostasis. Cancer cells are known to utilize lipids as building blocks for rapid proliferation. Therefore, we hypothesized that inhibition of SREBF1 leads to reduced cancer cell growth and progression. We used the Catalogue of Somatic Mutations in Cancer (COSMIC) to identify mutations in SREBF1 across different cancers. Using statistical and bioinformatics tools, we examined how mutation load correlates with tissue type, age, and pathogenicity to reveal the functional consequences of cancer-associated disruptions to SREBF1. Additionally, we used the fission yeast, Schizosaccharomyces pombe, to investigate the effects that disrupting the SREBF1 homolog, Sre1, have on viability, the DNA damage response (DDR), and lipid levels. When subjected to UV damage, cell viability decreases for both wildtype and sre1 mutant strains. However, the effect is more pronounced in the latter, indicating sre1 is required for the response to genotoxic stress. Furthermore, following DNA damage, lipid levels increased in the sre1 mutant relative to wild type cells, suggesting a role for Sre1 in keeping lipid abundance in conditions that favor cancer progression. Altogether, these data imply that regulation of lipid metabolism by Sre1 is important to deploy homeostatic balance in the aftermath of genotoxic insults.
