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Mazein2013 - Cholesterol biosynthesis pathway

ABSTRACT: No description

SUBMITTER: Alexander Mazein

PROVIDER: MODEL1409170000 | BioModels | 2015-04-15

REPOSITORIES: BioModels

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Publications

A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.

Mazein Alexander A Watterson Steven S Hsieh Wei-Yuan WY Griffiths William J WJ Ghazal Peter P

Biochemical pharmacology 20130410 1

Cholesterol biosynthesis serves as a central metabolic hub for numerous biological processes in health and disease. A detailed, integrative single-view description of how the cholesterol pathway is structured and how it interacts with other pathway systems is lacking in the existing literature. Here we provide a systematic review of the existing literature and present a detailed pathway diagram that describes the cholesterol biosynthesis pathway (the mevalonate, the Kandutch-Russell and the Bloc ...[more]

PMID: 23583456

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Viperin inhibits cholesterol biosynthesis and interacts with enzymes in the cholesterol biosynthetic pathway

Project description:Many enveloped viruses bud from cholesterol-rich lipid rafts on the cell membrane. Depleting cellular cholesterol impedes this process and results in viral particles with reduced viability. Viperin (virus inhibitory protein endoplasmic reticulum-associated, interferon-induced) is an ER membrane-associated enzyme that when expressed in response to viral infections exerts broad-ranging antiviral effects, including inhibiting the budding of some enveloped viruses. Here we have investigated the effect of viperin expression on cholesterol biosynthesis. We found that viperin expression reduces cholesterol levels by 20 – 30 % in HEK293T cells. A proteomic screen of the viperin interactome identified several cholesterol biosynthetic enzymes among the top hits. The two most highly enriched proteins were lanosterol synthase and squalene monooxygenase, enzymes that catalyze key steps establishing the sterol carbon skeleton. Co-immunoprecipitation experiments established that viperin, lanosterol synthase and squalene monooxygenase form a complex at the ER membrane. Co-expression of viperin was found to significantly inhibit the specific activity of lanosterol synthase in HEK293T cell lysates. Co-expression of viperin had no effect on the specific activity of squalene monooxygenase, but reduced its expression levels in the cells by approximately 30 %. Despite these inhibitory effects, co-expression of either LS or SM failed to reverse the viperin-induced depletion of cellular cholesterol levels in HEK293T cells. Our results establish a clear link between the down-regulation of cholesterol biosynthesis and viperin, although at this point the effect cannot be unambiguously attributed interactions between viperin and a specific biosynthetic enzyme.

2021-09-10 | PXD023999 | Pride

Podocalyxin-Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway

Project description:Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, we identify a membrane protein, Podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stems cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown-mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single-cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human-mouse chimeras, laminin and collagen signaling-related pathways are dominant in PODXL overexpressing cells. We conclude that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.

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A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.

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The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.

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Post-transcriptional air pollution oxidation to the cholesterol biosynthesis pathway promotes pulmonary stress phenotypes.

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Podocalyxin-Like Protein 1 Regulates Extended and Primed Pluripotency through the Cholesterol Biosynthesis Pathway

Project description:We utilized scRNA-seq to study the human-mouse chimera transcriptomic regulation at peri-implantation embryo stage. Single-cell RNA sequencing revealed PODXL overexpression boosted chimerism between human cells in mouse host embryos and the potential cell-cell communication interactions in human-mouse chimeras. Potential cell-cell communications were identified to optimize cell-cell contact interaction for reducing the xenogeneic barrier in the interspecies chimeras in future studies.

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Cholesterol Biosynthesis Modulates CSFV Replication

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Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.

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