Cloning, Expression, and Initial Characterization of a Novel Cytokine-like Gene Family

Zhu, Yujun; Xu, Gang; Patel, Arun H.; McLaughlin, Megan M.; Silverman, Carol; Knecht, Kristin; Sweitzer, Sharon; Li, Xiaotong; McDonnell, Peter; Mirabile, Rosanna C.; Zimmerman, Dawn; Boyce, Rogely; Tierney, Lauren A.; Hu, Erding; Livi, George P.; Wolf, Bryan A.; Abdel-Meguid, Sherin S.; Rose, George D.; Aurora, Rejeev; Hensley, Preston; Briggs, Michael D.; Young, Peter R.

doi:10.1006/geno.2002.6816

Cited by 172 publications

(206 citation statements)

References 20 publications

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“…Earlier works have revealed that ILEI acts downstream of TGF-b to induce epithelial-to-mesenchymal transition of epithelial cells, whereas PANDER, which is cosecreted with insulin from pancreatic islet cells, is involved in regulation of insulin secretion and glycemic levels 28,36,37 . Expression of the ILEI transcript in human brain has been described 22 . However, the function of ILEI in the nervous system remains largely unknown, except for its possible role in development of the Xenopus retina 38 is associated with an increased risk of AD 40 , and the neuronal expression of TGF-b type II receptors is reduced in AD brains from the early stage of disease development 31 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that ILEI is expressed in the central nervous system as well as in secretory epithelia 22,28 . However, the regional and cellular distribution of ILEI in mammalian brains has not been examined.…”

Section: Ilei Is a C-secretase Complex-binding Proteinmentioning

confidence: 99%

“…ILEI, which was originally identified in a database search for four-helix-bundle cytokines, is an evolutionarily conserved secretory protein 22 . ILEI is posttranslationally liberated from the membrane in secretory vesicles by cleavage of the signal sequence of the full-length (FL) precursor protein.…”

Section: Ilei Is a C-secretase Complex-binding Proteinmentioning

confidence: 99%

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The FAM3 superfamily member ILEI ameliorates Alzheimer’s disease-like pathology by destabilizing the penultimate amyloid-β precursor

et al. 2014

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Accumulation of amyloid-b peptide (Ab) in the brain underlies the pathogenesis of Alzheimer's disease (AD). Ab is produced by b-and g-secretase-mediated sequential proteolysis of amyloid-b precursor protein (APP). Here we identify a secretory protein named interleukinlike epithelial-mesenchymal transition inducer (ILEI, also known as FAM3 superfamily member C) as a negative regulator of Ab production. ILEI destabilizes the b-secretasecleaved APP carboxy-terminal fragment, the penultimate precursor of Ab, by binding to the g-secretase complex and interfering with its chaperone properties. Notch signalling and g-secretase activity are not affected by ILEI. We also show neuronal expression of ILEI and its induction by transforming growth factor-b signalling. The level of secreted ILEI is markedly decreased in the brains of AD patients. Transgenic (Tg) overexpression of ILEI significantly reduces the brain Ab burden and ameliorates the memory deficit in AD model mice. ILEI may be a plausible target for the development of disease-modifying therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Ilei Is a C-secretase Complex-binding Proteinmentioning

confidence: 99%

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The FAM3 superfamily member ILEI ameliorates Alzheimer’s disease-like pathology by destabilizing the penultimate amyloid-β precursor

et al. 2014

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“…Cytokine-like and unknown proteins-We have sequenced other cDNA (contig 28) whose sequences are similar to a cytokine-like protein that inhibits insulin secretion recently described (Zhu et al, 2002). This is the first description of this family of proteins in snake venoms.…”

Section: Growth Factors-in Our Library We Have Found Cluster 227 Thamentioning

confidence: 98%

“…This is the first description of this family of proteins in snake venoms. By immunohistochemistry it was shown that a member of this cytokine family was expressed prominently in the vascular endothelium, particularly in capillaries (Zhu et al, 2002). The function of this cytokine-like protein in snake venom remains to be determined, but it may be that it somehow affects vascular biology.…”

Section: Growth Factors-in Our Library We Have Found Cluster 227 Thamentioning

confidence: 99%

Bitis gabonica (Gaboon viper) snake venom gland: toward a catalog for the full-length transcripts (cDNA) and proteins

Francischetti

My-Pham

Harrison

et al. 2004

Gene

107

102

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The venom gland of the snake Bitis gabonica (Gaboon viper) was used for the first time to construct a unidirectional cDNA phage library followed by high-throughput sequencing and bioinformatic analysis. Hundreds of cDNAs were obtained and clustered into contigs. We found mostly novel full-length cDNA coding for metalloproteases (P-II and P-III classes), Lys49-phospholipase A2, serine proteases with essential mutations in the active site, Kunitz protease inhibitors, several C-type lectins, bradykinin-potentiating peptide, vascular endothelial growth factor, nucleotidases and nucleases, nerve growth factor, and L-amino acid oxidases. Two new members of the recently described short coding region family of disintegrin, displaying RGD and MLD motifs are reported. In addition, we have identified for the first time a cytokine-like molecule and a multi-Kunitz protease inhibitor in snake venoms. The CLUSTAL alignment and the unrooted cladograms for selected families of B. gabonica venom proteins are also presented. A significant number of sequences were devoid of database matches, suggesting that their biologic function remains to be identified. This paper also reports the N-terminus of the 15 most abundant venom proteins and the sequences matching their corresponding transcripts. The electronic version of this manuscript, available on request, contains spreadsheets with hyperlinks to FASTAformatted files for each contig and the best match to the GenBank and Conserved Domain Databases, in addition to CLUSTAL alignments of each contig. We have thus generated a comprehensive catalog of the B. gabonica venom gland, containing for each secreted protein: i) the predicted molecular weight, ii) the predicted isoelectric point, iii) the accession number, and iv) the putative function. The role of these molecules is discussed in the context of the envenomation caused by the Gaboon viper.

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Indels in the Evolution of the Human and Chimpanzee Genomes

Wetterbom¹,

Cavelier²,

Bergström³

2008

Encyclopedia of Life Sciences

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Mutations in the deoxyribonucleic acid (DNA) cause genomic divergence between species and provide a starting point for evolutionary change. There are several sources of sequence variation and here we will focus on insertions and deletions (indels). Such events occur frequently in genomic alignments of humans and chimpanzees and the indel divergence is estimated to 3–5%. In this article, we will discuss some causes behind indels and the possible impact of indels on the evolution of primate genomes. In addition, we will provide some examples of indels that may affect protein function as well as alternative splicing.

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Cloning, Expression, and Initial Characterization of a Novel Cytokine-like Gene Family

Cited by 172 publications

References 20 publications

The FAM3 superfamily member ILEI ameliorates Alzheimer’s disease-like pathology by destabilizing the penultimate amyloid-β precursor

The FAM3 superfamily member ILEI ameliorates Alzheimer’s disease-like pathology by destabilizing the penultimate amyloid-β precursor

Bitis gabonica (Gaboon viper) snake venom gland: toward a catalog for the full-length transcripts (cDNA) and proteins

Indels in the Evolution of the Human and Chimpanzee Genomes

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