title: Cholesterol biosynthesis and homeostasis in regulation of the cell cycle.
abstract: The cell cycle is a ubiquitous, multi-step process that is essential for growth and proliferation of cells. The role of membrane lipids in cell cycle regulation is not explored well, although a large number of cytoplasmic and nuclear regulators have been identified. We focus in this work on the role of membrane cholesterol in cell cycle regulation. In particular, we have explored the stringency of the requirement of cholesterol in the regulation of cell cycle progression. For this purpose, we utilized distal and proximal inhibitors of cholesterol biosynthesis, and monitored their effect on cell cycle progression. We show that cholesterol content increases in S phase and inhibition of cholesterol biosynthesis results in cell cycle arrest in G1 phase under certain conditions. Interestingly, G1 arrest mediated by cholesterol biosynthesis inhibitors could be reversed upon metabolic replenishment of cholesterol. Importantly, our results show that the requirement of cholesterol for G1 to S transition is absolute, and even immediate biosynthetic precursors of cholesterol, differing with cholesterol merely in a double bond, could not replace cholesterol for reversing the cell cycle arrest. These results are useful in the context of diseases, such as cancer and Alzheimer's disease, that are associated with impaired cholesterol biosynthesis and homeostasis.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.
authors.forename: Pushpendra
authors.initials: P
authors.lastname: Singh
authors.forename: Roopali
authors.initials: R
authors.lastname: Saxena
authors.forename: Gunda
authors.initials: G
authors.lastname: Srinivas
authors.forename: Gopal
authors.initials: G
authors.lastname: Pande
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D048429:Cell Size; D002784:Cholesterol / Q000096:biosynthesis*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008148:Lovastatin / Q000494:pharmacology; D051381:Rats; D014308:Triparanol / Q000494:pharmacology
chemical_list: D014308:Triparanol; D002784:Cholesterol; D008148:Lovastatin
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