A mutation in the c-fos gene associated with congenital generalized lipodystrophy.

Background: Congenital generalized lipodystrophy (CGL) or Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare genetic syndrome characterized by the absence of adipose tissue. As CGL is thought to be related to malfunctions in adipocyte development, genes involved in the mechanisms of adipocyte biology and maintenance or differentiation of adipocytes, especially transcription factors are candidates. Several genes (BSCL1-4) were found to be associated to the syndrome but not all CGL patients carry mutations in these genes.

Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes.

Objective: Increased lipid accumulation in cells and tissues is a key phenomenon in the development of obesity, insulin resistance, and atherosclerosis. In the regulation of lipid content of cells and tissues the SREBPs play a dominant role as transcription factors.

Methods: Since growth hormone (GH) affects lipid metabolism and function of fat as well as liver cells, we have investigated the role of SREBP-1a, SREBP-1c and SREBP-2 in the gene regulatory action of GH in the human liver cell line HepG2 and primary mouse hepatocytes.

Effect of sterol regulatory element binding protein-1a on the mitochondrial protein pattern in human liver cells detected by 2D-DIGE.

Sterol regulatory element binding protein-1a (SREBP-1a) is a transcription factor that is a major player in lipid metabolism and insulin action. We have generated human liver cells (HepG2) overexpressing active SREBP-1a constitutively called SREBP-1a (+). These cells show massive intracellular lipid accumulation.

Identification of major ERK-related phosphorylation sites in Gab1.

Gab1 (Grb2-associated binder1) belongs to a family of multifunctional docking proteins that play a central role in the integration of receptor tyrosine kinase (RTK) signaling, i.e., mediating cellular growth response, transformation, and apoptosis.

Insulin-activated Erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding Protein-2 at serine residues 432 and 455 in vivo.

The transcription factor sterol regulatory element binding protein (SREBP)-2 plays a pivotal role in lipid metabolism. Previously, we have shown that the mature form of SREBP-2 is a substrate of Erk-mitogen-activated protein kinases (MAPK). The aim of the present study was to identify Erk-specific phosphorylation sites.

Estrogen receptor-alpha and Sp1 interact in the induction of the low density lipoprotein-receptor.

Both estrogen and selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene have been demonstrated to lower plasma low density lipoprotein (LDL)-cholesterol concentrations by stimulation of LDL receptor gene expression. To determine the molecular mechanisms of estradiol- and tamoxifen-induced LDL receptor expression, we performed transient transfection experiments with luciferase reporter gene-constructs under transcriptional control of the human LDL receptor promoter. We demonstrate, that estradiol and tamoxifen stimulate LDL receptor gene expression in human HepG2 hepatoma cells only when estrogen receptor (ER)-alpha but not when ER-beta is cotransfected.