The site-2 protease

AbstractThe site-2 protease (S2P) is an unusually-hydrophobic integral membrane protease. It cleaves its substrates, which are membrane-bound transcription factors, within membrane-spanning helices. Although structural information for S2P from animals is lacking, the available data suggest that cleavage may occur at or within the lipid bilayer. In mammalian cells, S2P is essential owing to its activation of the sterol regulatory element binding proteins (SREBPs); in the absence of exogenous lipid, cells lacking S2P cannot survive. S2P is also important in the endoplasmic reticulum (ER) stress response, activating several different membrane-bound transcription factors. Human patients harboring reduction-of-function mutations in S2P exhibit an array of pathologies ranging from skin defects to neurological abnormalities. Surprisingly, Drosophila melanogaster lacking S2P are viable and fertile. This article is part of a Special Issue entitled: Intramembrane Proteases

Expression and Characterization of Drosophila Signal Peptide Peptidase-Like (sppL), a Gene That Encodes an Intramembrane Protease

Intramembrane proteases of the Signal Peptide Peptidase (SPP) family play important roles in developmental, metabolic and signaling pathways. Although vertebrates have one SPP and four SPP-like (SPPL) genes, we found that insect genomes encode one Spp and one SppL. Characterization of the Drosophila sppL gene revealed that the predicted SppL protein is a highly conserved structural homolog of the vertebrate SPPL3 proteases, with a predicted nine-transmembrane topology, an active site containing aspartyl residues within a transmembrane region, and a carboxy-terminal PAL domain. SppL protein localized to both the Golgi and ER. Whereas spp is an essential gene that is required during early larval stages and whereas spp loss-of-function reduced the unfolded protein response (UPR), sppL loss of function had no apparent phenotype. This was unexpected given that genetic knockdown phenotypes in other organisms suggested significant roles for Spp-related proteases

Sudden infant death syndrome in the Middle East: An exploration of the literature on rates, risk factors, high risk groups and intervention programs

Sudden Infant Death Syndrome (SIDS) is a problem world-wide. Since it was identified; Western nations have implemented extensive SIDS education campaigns to reduce SIDS risk which have resulted in dramatically decreasing SIDS death rates. In contrast, there is little information available about the impact of SIDS in Middle East (ME) countries where high infant mortality is common. STo investigate SIDS incidence rates across various ME countries, ascertain specific SIDS risk factors relevant to ME populations, categorise high risk groups and identify SIDS intervention programs in the ME. A structured literature review was performed. A total of 10,509 study were identified with 11 proving to be most relevant to the research purpose. The SIDS incidence rates data available in ME countries is extremely limited with only five studies addressing SIDS rates in the ME. For a range of reasons, many infant deaths are registered as "cause unknown" with no associated autopsy report or other details. Additionally, limitations in the study designs restrict the ability to accurately estimate incidence rates from the research projects reported. The most significant risk factor for SIDS in ME countries identified in the literature is the high incidence of smoking, resulting from less political restrictions on smoking at home and public settings. Targeted public health SIDS education programs need to be developed and promoted in high risk ME countries with a specific focus on infant care practices, lifestyle and general living conditions