Other ways to skin a cat Activating SREBP without Scap

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Fly (Impact Factor: 3.33). 01/2010; 5(1):3-6. DOI: 10.4161/fly.5.1.13475
Source: PubMed


The sterol regulatory element binding protein (SREBP) pathway plays a central role in the global regulation of lipid homeostasis. SREBPs are membrane-bound transcription factors whose proteolytic activation is regulated by cellular lipid levels; when demand for lipid rises, SREBP travels from the endoplasmic reticulum to the Golgi apparatus where it is cleaved by two distinct proteases. Cleavage releases the transcription factor domain of SREBP from the membrane-bound precursor and transcription of its target genes consequently rises. Previously, we isolated Drosophila mutants null for dsrebp and others lacking site-2 protease (ds2p), the second of two Golgi-resident proteases that cleave dSREBP. dScap is a protein needed to escort dSREBP from the ER to the Golgi apparatus. We recently characterized the phenotypes of dscap mutants as well. Here, we describe additional details of phenotypes arising from the inability to activate SREBP appropriately.

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Available from: Robert B Rawson, Jul 07, 2014
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    ABSTRACT: The class Insecta has more than 1 million different cataloged species living in almost all habitats throughout the world, and they encompass many different lifestyles. Understanding how these animals evolved in terms of their physiology and biochemistry is reason enough to perform research in the basic science field. However, hematophagous insects spread vector-borne diseases, such as malaria, dengue fever and Chagas’ disease through human populations living in tropical regions. In addition, the herbivorous species can damage plantation fields, leading to both reduced production and economic losses. Moreover, insects can be easily raised in laboratory colonies, and some can be readily genetically manipulated. Finally, some similarities between insect and mammalian physiology make these invertebrates excellent models to study human problems; for example, lipid metabolism deregulation, which can be responsible for the development of diseases such as obesity, arteriosclerosis and diabetes, one of the major health problems concerning the Western population. For all the above reasons, research groups around the world are working with insect models to generate data that can be used to control disease vectors and agricultural pests and may even help to understand human metabolism. Here, we will review the findings achieved in insect lipid metabolism, particularly over the last 10 years, and we will focus on how genes involved in these pathways are regulated. We will discuss how different environmental signals or metabolites and hormones produced by insects can control the activity of transcription factors to change gene expression profiles. The gaps found in our current knowledge and possible future directions in this research field are also discussed.
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