RSK2 in Homeostasis
| dc.contributor.committeeChair | Lannigan, Deborah A | |
| dc.contributor.committeeMember | Duvall, Craig | |
| dc.contributor.committeeMember | Brunger, Jonathan | |
| dc.contributor.committeeMember | Blind, Ray | |
| dc.contributor.committeeMember | Stafford, John | |
| dc.creator | Wright, Eric Brandon | |
| dc.creator.orcid | 0000-0001-9575-6801 | |
| dc.date.accessioned | 2025-06-06T09:45:46Z | |
| dc.date.created | 2025-05 | |
| dc.date.issued | 2024-12-04 | |
| dc.date.submitted | May 2025 | |
| dc.description.abstract | The p90 ribosomal S6 kinase 2 (RSK2) is a serine/threonine protein kinase activated by extracellular signal-regulated kinase 1/2 (ERK1/2) whose physiological functions are not fully understood. We found that loss of RSK2 results in decreased litter size and underweight pups. In an effort to understand these fertility issues serum lipid levels were analyzed and serum triacylglyceride (TAG) levels were found to be decreased in female RSK2 knockout (RSK2KO) mice compared to wild type (WT). TAG levels are important regulators of fertility with the liver being the major organ involved in TAG metabolism. In support of a defect in liver lipid metabolism, TAG levels were also found to be reduced in the livers of female RSK2KO mice. Transcriptomic analysis of livers from female RSK2KO mice, staged during high estrogen levels, showed decreased expression of genes involved in de novo lipogenesis (DNL). These results were validated by qrtPCR. DNL is regulated by the transcription factor sterol response element binding protein 1c (SREBP1c), whose mRNA expression levels did not change. SREBP1c activity is tightly regulated and studies on the mechanism of RSK2 regulation of DNL are ongoing. DNL is regulated in an estrogen-dependent manner and interestingly, loss of RSK2 eliminated the increase in DNL that occurs in response to estrogen signaling. Transcriptomic and qrtPCR analysis showed that RSK2 increases the expression of ESR1, the gene encoding estrogen receptor alpha (ER), during high estrogen levels. We propose that RSK2 drives estrogen signaling in the liver through regulation of ER mRNA levels by a mechanism that is currently being investigated. TAG levels are essential for fertility and we hypothesize that RSK2 regulates fertility through control of DNL in the liver. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/1803/19749 | |
| dc.language.iso | en | |
| dc.subject | RSK2 | |
| dc.subject | p90 ribosomal s6 kinase | |
| dc.subject | estrogen | |
| dc.subject | de novo lipogenesis | |
| dc.subject | fertility | |
| dc.title | RSK2 in Homeostasis | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.lift | 2027-05-01 | |
| local.embargo.terms | 2027-05-01 | |
| thesis.degree.discipline | Biomedical Engineering | |
| thesis.degree.grantor | Vanderbilt University Graduate School | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | PhD |
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