Genome-wide association studies (GWAS) have linked single-nucleotide polymorphisms (SNPs) with type 2 diabetes (T2D). Mice overexpressing have elevated cholesterol levels when fed a diet that induces hepatic steatosis. These and other studies suggest an important role for insulin growth factor 2 mRNA binding protein 2 (IGF2BP2) in the initiation and progression of several metabolic disorders.
View Article and Find Full Text PDFMetabolic syndrome (MetS) is a term used to characterize individuals having at least three of the following diseases: obesity, dyslipidemia, hyperglycemia, insulin resistance, hypertension, and nonalcoholic fatty liver disease (NAFLD). It is widespread, and the number of individuals with MetS is increasing. However, the events leading to the manifestation of MetS are not well-understood.
View Article and Find Full Text PDFCeramides and sphingolipid intermediates are well-established regulators of the cell cycle. In the budding yeast Saccharomyces cerevisae, the complex sphingolipid backbone, ceramide, comprises a long chain sphingoid base, a polar head group, and a very long chain fatty acid (VLCFA). While ceramides and long chain bases have been extensively studied as to their roles in regulating cell cycle arrest under multiple conditions, the roles of VLCFAs are not well understood.
View Article and Find Full Text PDFis an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to pathogenicity. strains lacking CaArv1 are avirulent.
View Article and Find Full Text PDFSphingolipids are major constituents of membranes. A number of S. cerevisiae sphingolipid intermediates such as long chains sphingoid bases (LCBs) and ceramides act as signaling molecules regulating cell cycle progression, adaptability to heat stress, and survival in response to starvation.
View Article and Find Full Text PDFUsing yeast two-hybrid analysis, we identified several novel protein interactions for the oncoprotein Cancerous Inhibitor of PP2A (CIP2A) and confirmed a subset of these interactions in human cancer cell lines. Analysis of the interaction in prostate carcinoma cells between CIP2A and leucine-rich repeat-containing protein 59 (LRRC59) suggests that CIP2A is translocated into the nucleus at G2/M through its association with LRRC59. Recent work by others has demonstrated that nuclear CIP2A disrupts mitotic checkpoints, which promotes deregulation of the cell cycle and increases cancerous phenotypes.
View Article and Find Full Text PDFYeast two-hybrid (Y2H) studies have shown that cancerous Inhibitor of protein phosphatase 2A (CIP2A) interacted with several proteins, including leucine-rich repeat-containing protein 59 (LRRC59), suggesting that CIP2A may interact with the chromosome maintenance protein, shugoshin (Sgol1). We previously showed that LRRC59 interacted with CIP2A, which was required for CIP2A nuclear localization. Thus, we predicted that CIP2A and Sgol1 may also interact.
View Article and Find Full Text PDFAMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive.
View Article and Find Full Text PDFDysregulation of cholesterol homeostasis is associated with various metabolic diseases, including atherosclerosis and type 2 diabetes. The sterol response element binding protein (SREBP)-2 transcription factor induces the expression of genes involved in de novo cholesterol biosynthesis and low density lipoprotein (LDL) uptake, thus it plays a crucial role in maintaining cholesterol homeostasis. Here, we found that overexpressing microRNA (miR)-185 in HepG2 cells repressed SREBP-2 expression and protein level.
View Article and Find Full Text PDFSaccharomyces cerevisiae ergosterol biosynthesis, like cholesterol biosynthesis in mammals, is regulated at the transcriptional level by a sterol feedback mechanism. Yeast studies defined a 7-bp consensus sterol-response element (SRE) common to genes involved in sterol biosynthesis and two transcription factors, Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes. The 7-bp consensus SRE is identical to the anaerobic response element, AR1c.
View Article and Find Full Text PDFMaintaining accurate progression through the cell cycle requires the proper temporal expression and regulation of cyclins. The mammalian D-type cyclins promote G1-S transition. D1 cyclin protein stability is regulated through its ubiquitylation and resulting proteolysis catalyzed by the SCF E3 ubiquitin ligase complex containing the F-box protein, Fbx4.
View Article and Find Full Text PDFThe lipid transporter Arv1 regulates sterol trafficking, and glycosylphosphatidylinositol and sphingolipid biosyntheses in Saccharomyces cerevisiae. ScArv1 contains an Arv1 homology domain (AHD) that is conserved at the amino acid level in the pathogenic fungal species, Candida albicans and Candida glabrata. Here we show S.
View Article and Find Full Text PDFProtein phosphatase 2A (PP2A) is a heterotrimer consisting of A and B regulatory subunits and a C catalytic subunit. PP2A regulates mitotic cell events that include the cell cycle, nutrient sensing, p53 stability and various mitogenic signals. The role of PP2A during meiosis is less understood.
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