Non-genomic regulation of lipid synthesis by the protein c-Fos

CAPUTTO BL

Banff

Conferencia; ASBMB Special Symposia Series joint meeting with International Conference on the Bioscience of Lipids; 2012

ASBMB Special Symposia Series joint meeting with ICBL

Non-genomic regulation of lipid synthesis by the protein c-Fos. BL Caputto - CIQUIBIC - Dpto. Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ARGENTINA. e mail: bcaputto@fcq.unc.edu.ar Herein, we will discuss some insights into the activation and/or recruitment of regulatory enzymes to membranes and the molecular mechanisms involved, putting special emphasis on c-Fos, a protein that has deserved less attention so far and that has a solid background of data supporting its participation in lipid synthesis activation required for cell growth and proliferation. In addition, the enzymes Lipin and CCT of the pathway of synthesis of phospholipids, taken as examples of diverse non-genomic regulatory mechanisms that occur via translocation or conformational changes of these enzymes will be given. These rapidly-induced changes are mediated by an intrinsic property of the enzyme that senses lipid composition, by posttranslational modifications or both. Another non-genomic lipid synthesis regulation mechanism that will be discussed is mediated by an Immediate Early Gene protein: c-Fos. In its canonical function, c-Fos is a well established transcription factor member of the AP-1 family. Herein, it is discussed some of the results that led to the hypothesis that c-Fos activates global phospholipid synthesis and that this activation is crucial to support membrane biogenesis demands required for cell processes such as proliferation and differentiation. This c-Fos-dependent lipid synthesis activation is achieved by a non-genomic mechanism, that is, its N-terminal domain mediates its physical association to particular lipid synthesizing enzymes whereas its basic Domain (aa 139-159) activates these enzymes. This c-Fos/endoplasmic reticulum association is ultimately regulated by the phosphorylation status of tyrosines #10 and #30 of c-Fos. Other possible mechanisms involved in phospholipid synthesis activation by c-Fos, such as disorder-to-order transitions or membrane lipid sensing are also discussed. The balance between regulation of enzymes by translocation/ posttranslational modifications during cellular proliferation or growth versus c-Fos-dependent regulation will, by no doubt, have to be the focus of future studies.