Prediction of the Coding Sequences of Unidentified Human Genes. XIX. The complete Sequences of 100 New cDNA Clones from Brain Which Code for Large Proteins in vitro

Nagase, Takahiro; Kikuno, Reiko; Hattori, Atsushi; Kondo, Yasumitsu; Okumura, Koji; Ohara, Osamu

doi:10.1093/dnares/7.6.347

Cited by 100 publications

(81 citation statements)

References 12 publications

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“…A large sequencing project first identified the coding sequence for fibrillin-3 in a human brain cDNA library (Nagase et al, 2001). Subsequently, Corson et al reported strong expression of fibrillin-3 in human fetal brain based on RT-PCR and Northern blotting (Corson et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Fibrillin-3 expression in human development

et al. 2011

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Fibrillin proteins are the major components of extracellular microfibrils found in many connective tissues. Fibrillin-1 and fibrillin-2 are well studied and mutations in these proteins cause a number of fibrillinopathies including Marfan syndrome and congenital contractural arachnodactyly, respectively. Fibrillin-3 was more recently discovered and is much less well characterized. Fibrillin-1 is expressed throughout life, whereas fibrillin-2 and -3 are thought to be primarily present during development. Here, we report detailed fibrillin-3 expression patterns in early human development.A polyclonal antiserum against a C-terminal recombinant half of human fibrillin-3 was produced in rabbit. Anti-fibrillin-3 antibodies were affinity-purified and antibodies cross-reacting with the other fibrillins were removed by absorption resulting in specific anti-fibrillin-3 antibodies. Immunohistochemical analyses with these purified antibodies demonstrate that fibrillin-3 is temporally expressed in numerous tissues relatively evenly from the 6 th to the 12 th gestational week. Fibrillin-3 was found spatially expressed in perichondrium, perineurium, perimysium, skin, developing bronchi, glomeruli, pancreas, kidney, heart and testis and at the prospective basement membranes in developing epithelia and endothelia. Double immunohistochemical analyses showed that all fibrillins are globally expressed in the same organs, with a number of differences on the tissue level in cartilage, perichondrium and developing bronchi. These results suggest that fibrillin-3, compared to the other fibrillins, fulfills both overlapping and distinct functions in human development.

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Section: Discussionmentioning

confidence: 99%

“…The cDNA coding for fibrillin-3 has first been isolated from human fetal brain (Nagase et al, 2001). Corson and coworkers subsequently found that fibrillin-3, similar to fibrillin-2, is mainly expressed during embryonic development (Corson et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Fibrillin-3 expression in human development

et al. 2011

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“…Our observation of a frequent mutant allele LOH in the region telomeric to MLH1, in particular, implicated this region as a possible location of additional targets for LOH irrespective of MLH1. Potential target genes include DCAMKL3 (KIAA1765), which has doublecortin and CaM-kinase-like 3 motifs and may function in cell signaling (Nagase et al, 2000;Ohmae et al, 2006), and STAC (SRC homology 3 and cysteine-rich domain), which may play a role in cell proliferation, transformation and apoptosis (Suzuki et al, 1996;Satoh et al, 2006). The region at 3p21-22 is often deleted in human epithelial malignancies (Protopopov et al, 2003), and future studies should examine if DCAMKL3 or STAC, or other genes from this region, are directly involved in these tumorigenic processes.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of inactivation of MLH1 in hereditary nonpolyposis colorectal carcinoma: a novel approach

et al. 2007

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Mutations in the DNA mismatch repair gene MLH1 are a major cause of hereditary nonpolyposis colorectal cancer (HNPCC). No mutant phenotype is observed before the wild-type (wt) allele is somatically inactivated in target tissue. We addressed the mechanisms of MLH1 inactivation in 25 colorectal (CRC) and 32 endometrial cancers (ECs) from MLH1 mutation carriers (Mut1, in-frame genomic deletion; Mut2, out-of-frame splice site mutation; Mut3, missense mutation). By a quantitative method, matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF), utilizing four intragenic single nucleotide polymorphisms and mutations, loss of heterozygosity (LOH) was present in 31/57 (54.4%) of tumors. The wt allele displayed LOH more often than the mutant allele (23/57 vs 8/57, P ¼ 0.006). For Mut1, LOH was more frequent in CRC than EC (10/11 vs 1/13, Po0.0001), whereas Mut2 and Mut3 displayed opposite LOH pattern. Moreover, although wt LOH predominated in CRC irrespective of the predisposing mutation, LOH often affected the mutant allele in EC from Mut2 and Mut3 carriers (6/19, 31.6%). MLH1 promoter methylation, which reflected a more widespread hypermethylation tendency, occurred in 4/55 (7.3%) of tumors and was inversely associated with LOH. In conclusion, the patterns of somatic events (LOH and promoter methylation) differ depending on the tissue and germline mutation, which may in part explain the differential tumor susceptibility of different organs in HNPCC. MALDI-TOF provides a novel approach for the detection and quantification of LOH.

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“…Production of the N-and C-terminal fragments of human fibrillin-1 (rFBN1-N, rFBN1-C, respectively) and fibrillin-2 (rFBN2-N, rFBN2-C, respectively) has been described in detail previously (Jensen et al, 2001;Lin et al, 2002). To produce a new recombinant C-terminal half of human fibrillin-3 (rFBN3-C; D 1321 -R 2684 ), the cDNA for human fibrillin-3 (clone KIAA1776, Nagase et al, 2001) was obtained from the Kazusa DNA Research Institute (Chiba, Japan) and cloned into the pBluescript II SK(ϩ) plasmid (Stratagene, La Jolla, CA). The resulting plasmid pBS-FBN3 was cut with NheI ϫ SgrAI and the 7888-base pair fragment was ligated with the complementary oligonucleotides 5Ј-CTAGCAGACCTGGATGAATGAATG-CATCTCCCAGGAGCA-3Ј and 5Ј-CCGGTGCTTGGGAGATGCATTCATC-CAGGTCTG-3Ј generating a NheI restriction site at the 5Ј end (pBS-rFBN3C-1).…”

Section: Proteinsmentioning

confidence: 99%

Fibrillin Assembly Requires Fibronectin

Sabatier

Chen²,

Fagotto‐Kaufmann³

et al. 2009

MBoC

224

240

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Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and nonelastic extracellular matrices. Proper assembly mechanisms are central to the formation and function of these microfibrils, and their properties are often compromised in pathological circumstances such as in Marfan syndrome and in other fibrillinopathies. Here, we have used human dermal fibroblasts to analyze the assembly of fibrillin-1 in dependence of other matrix-forming proteins. siRNA knockdown experiments demonstrated that the assembly of fibrillin-1 is strictly dependent on the presence of extracellular fibronectin fibrils. Immunolabeling performed at the light and electron microscopic level showed colocalization of fibrillin-1 with fibronectin fibrils at the early stages of the assembly process. Protein-binding assays demonstrated interactions of fibronectin with a C-terminal region of fibrillin-1, -2, and -3 and with an N-terminal region of fibrillin-1. The C-terminal half of fibrillin-2 and -3 had propensities to multimerize, as has been previously shown for fibrillin-1. The C-terminal of all three fibrillins interacted strongly with fibronectin as multimers, but not as monomers. Mapping studies revealed that the major binding interaction between fibrillins and fibronectin involves the collagen/ gelatin-binding region between domains FNI 6 and FNI 9 . INTRODUCTIONFibrillins are extracellular matrix components with important functions in elastic and nonelastic tissues including blood vessels, bone, and the eye. Fibrillins, together with the latent transforming growth factor-␤ (TGF-␤)-binding proteins (LTBPs), constitute the fibrillin-LTBP family of proteins (Hubmacher et al., 2006). Fibrillins are ϳ350 kDa in size, are disulfide-rich and glycosylated, and have a characteristic modular structure. The three human fibrillinsfibrillin-1, -2, and -3 -are encoded by different genes and are conserved at the amino acid level both in relation to one another and among species. Fibrillins are mainly composed of tandem arrays of calcium-binding epidermal growth factor-like domains interspersed with TGF-␤-binding protein domains (TB/8-Cys) and hybrid domains Hubmacher et al., 2006). Mutations in fibrillins give rise to the so-called fibrillinopathies, which include Marfan syndrome and autosomal dominant Weill-Marchesani syndrome, both caused by mutations in fibrillin-1, and Beal's syndrome, caused by mutations in fibrillin-2 (Robinson et al., 2006).High-molecular-weight, multiprotein assemblies called microfibrils are the functional units of fibrillins, which serve as a scaffold for the biogenesis of elastic fibers, confer structural integrity to individual organ systems, regulate growth factor signaling of TGF-␤-bone morphogenic protein (BMP) superfamily members and provide limited elasticity to tissues (Kielty et al., 2002;Charbonneau et al., 2004;Ramirez and Dietz, 2007). Extracted microfibrils from cell culture or tissues display a typical bead-on-a-string ultrastructure, having a 50 -55-nm periodicity when analyzed by ele...

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Prediction of the Coding Sequences of Unidentified Human Genes. XIX. The complete Sequences of 100 New cDNA Clones from Brain Which Code for Large Proteins in vitro

Cited by 100 publications

References 12 publications

Fibrillin-3 expression in human development

Fibrillin-3 expression in human development

Mechanisms of inactivation of MLH1 in hereditary nonpolyposis colorectal carcinoma: a novel approach

Fibrillin Assembly Requires Fibronectin

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