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Life Sciences Commons

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Biochemistry, Biophysics, and Structural Biology

Wright State University

Theses/Dissertations

2018

Molecular Biology

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Full-Text Articles in Life Sciences

Lipin1 Regulates Skeletal Muscle Differentiation Through The Pkc/Hdac5/Mef2c:Myod -Mediated Pathway, Abdulrahman M. Jama Jan 2018

Lipin1 Regulates Skeletal Muscle Differentiation Through The Pkc/Hdac5/Mef2c:Myod -Mediated Pathway, Abdulrahman M. Jama

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Our previous characterization of global lipin1-deficient (fld) mice demonstrated that lipin1 played a novel role in skeletal muscle (SM) regeneration. The clinical relevance of lipin1 has been observed in patients with lipin1 null mutations where they exhibited severe rhabdomyolysis with aggregated and dysfunctional mitochondria. Lipin1 is a key gene that plays an important role in lipid biosynthesis and metabolism. It has dual functions as it contains a phosphatase activity that converts phosphatidic acid (PA) to diacylglycerol (DAG), the penultimate step in triglycerides (TAG) biosynthesis as well as transcriptional co-activator function. In the cytosol and ER, lipin1 carries out its lipid …


Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido Jan 2018

Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido

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Ras proteins are small GTPases that regulate cell growth, differentiation and apoptosis. There are three main isoforms: H-, N-, and K-Ras in mammalian cells, and they cycle between an active GTP- and inactive GDP-bound states. Constitutively active Ras mutations are found in ~15% of all human cancers. Of those, oncogenic K-Ras is found in ~98% of pancreatic, ~52% colorectal, and ~32% of lung cancers. In nearly 30 years since its discovery, there are no anti-K-Ras drugs currently available for clinical use. Since K-Ras must be localized to the plasma membrane (PM) for its full biological activity, targeting K-Ras PM interaction …