Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated cDNAs and completed for the first time the primary structure for a novel collagenous chain that was partially characterized earlier and named alpha 1(Y) chain [Yoshioka, H. et al. (1992) Genomics 13, 884-886]. The size of the coding region was unexpectedly small compared with the length of the mRNA (> 10 kb), owing to the presence of a long 3' untranslated region (> 5 kb). The predicted polypeptide contained 1,142 amino acid residues with a 23-residue signal peptide consisting of 5 collagenous domains of 70-224 residues in length, interspersed and flanked with 6 noncollagenous (NC) domains. The primary structure is distinct from those of the 32 known collagen alpha-chains of types I through XVIII. Therefore, we designate this newly discovered collagen chain the alpha 1 chain of type XIX collagen. Sequence analysis suggested that this chain belongs to the recently discovered group of collagens known as FACITs (fibril associated collagens with interrupted triple-helices). Northern blotting analysis demonstrated hybridization of the cDNA to a large mRNA species (> 10 kb) extracted from a rhabdomyosarcoma cell line (CCL 136). We also isolated numerous truncated cDNA clones of which the 3' parts were different from the "proto" type of the mRNA of > 10-kb size. Sequence comparison between cDNAs and corresponding genomic DNA fragments indicated that unusual splicing events occurred through insufficient recognition at acceptor sites. Expression of the gene was extremely infrequent in the rhabdomyosarcoma cell line; it could be restricted to certain animal tissues both temporally and spatially during early development.
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PMID:The mRNA for alpha 1(XIX) collagen chain, a new member of FACITs, contains a long unusual 3' untranslated region and displays many unique splicing variants. 777 80

We previously isolated a clone from a human rhabdomyosarcoma (RH) cDNA library coding for a collagen chain different from those constituting the 18 reported types (Myers, J. C., Sun, M. J., D'Ippolito, J. A., Jabs, E. W., Neilson, E. G., and Dion, A. S. (1993) Gene (Amst.) 123, 211-217). The sequence translated to a 186-amino acid noncollagenous region, a 524-residue three-subdomain collagenous region, and a presumed 8-amino acid COOH-terminal peptide. To further elucidate the primary structure of this collagen, we have now determined the sequence of additional cDNA clones. Overlapping 3' clones, found to diverge exactly where the noncollagenous 8-residue COOH sequence began, encode two additional collagenous subdomains of 168 and 70 residues and a 19-residue COOH-terminal peptide. Analysis of genomic DNA spanning the region in question revealed several 45- and 51-base pair exons linked by 4 introns totaling over 5 kilobases (kb). A 2-kb intron, absent from the clones coding for the extended collagenous region, was used in Northern blot hybridization to detect an apparently prevalent splicing intermediate 2 kb larger than the major 12.4-kb RH transcript. Therefore, the triple-helical region of this collagen chain is likely to be composed of 832 amino acids divided into five collagenous subdomains separated by 20-44 residue interruptions. Two interruptions are similar in sequence and position to those located in the type XVI chain. Furthermore, the arrangement of 2 cysteines near the COOH terminus and two imperfections in collagenous subdomain 1 are conserved in the related subclass composed of type IX, XII, XIV, and XVI collagens. However, in contrast to the COOH-terminal interchain bridging in this latter collagen group, molecular modeling strongly predicts that the cysteines in RH collagen participate in intrachain disulfide bonds. Taken together, the data clearly show that RH collagen does not represent another chain of one of the known collagen types. We propose that it be designated the alpha 1 chain of type XIX collagen.
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PMID:The triple-helical region of human type XIX collagen consists of multiple collagenous subdomains and exhibits limited sequence homology to alpha 1(XVI). 803 3

Nineteen types, the product of 33 genes, comprise the collagen family of proteins. Types I, II, III, V, and XI constitute the fibrillar collagens, whereas types IV, VI to X, and XII to XIX represent the structurally diverse, nonfibrillar members. Type XIX collagen was discovered from the sequence of rhabdomyosarcoma cDNA clones. The type XIX chain consists of 1142 amino acids that contribute primarily to a unique five subdomain triple-helical region. To characterize the protein, to determine the tissue distribution, and to provide some insight into its function, we generated two type XIX-specific polyclonal antibodies. One was directed against a recombinant molecule containing amino-terminal sequences, and the second was derived from a synthetic peptide corresponding to most of the short carboxy terminus. These antibodies were used in immunoblot assays of rhabdomyosarcoma cell/matrix homogenates to identify a 165-kd disulfide-bonded and bacterial collagenase-sensitive protein. Immunohistochemical analysis of type XIX collagen was performed for human skeletal muscle, spleen, prostate, kidney, liver, placenta, colon, and skin. In contrast to Northern blot hybridizations, which showed very low levels of the 12-kb transcript in few tissues, the protein was found in all tissues examined. The type XIX collagen distribution was restricted to vascular, neuronal, mesenchymal, and some epithelial basement membrane zones, which is similar to the profile recently established (Ref. 8) and further extended here for type XV collagen. Nevertheless, localization of type XIX exhibited significant differences from type XV collagen that were particularly evident in the kidney, liver, and spleen. This report, in conjunction with the type XV results and other studies of type XVIII collagen, indicates the existence of a new collagen subgroup founded on their widespread presence in basement membrane zones regardless of chain homology. In addition to their role in basement membrane-stromal interactions, the pronounced vascular association suggests involvement of these related collagen types with angiogenic and pathological processes.
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PMID:Biochemical and immunohistochemical characterization of human type XIX defines a novel class of basement membrane zone collagens. 940 23

Rhabdomyosarcomas are known to recapitulate some of the early events in skeletal muscle embryogenesis, and cultures derived from these tumors have been extensively used to elucidate processes associated with the differentiation of primitive mesenchymal cells. These neoplasms have also provided important systems for studying different collagen types. This aspect is particularly relevant to type XIX collagen, which was originally identified from rhabdomyosarcoma cDNA clones. Although this collagen has been localized in vivo to basement membrane zones in a wide variety of tissues, including skeletal muscle, the tumor cells appear to be a unique source of its expression in vitro. We have found that one particular cell line-derived from a peritesticular embryonal rhabdomyosarcoma-produced relatively large amounts of type XIX collagen, especially in those rare instances in which these cells appear to spontaneously differentiate. To characterize this phenomenon, tumor cells were grown under conditions known to induce differentiation in normal myoblast cultures. In response to this treatment, the typical tumor cell morphology consistently and reproducibly switched from polygonal to round/spindle-shaped with the subsequent appearance of some structures resembling myotubes. Concurrently, the cultures commenced a dramatic up-regulation of type XIX collagen and skeletal muscle myosin heavy chain and alpha-actinin in a time-dependent fashion, whereas protein and mRNA levels of other matrix proteins were either decreased or unchanged. Moreover, immunocytochemical analysis revealed that only a subpopulation of the cells was responsible for the increased synthesis of type XIX collagen, alpha-actinin, and myosin, and that the same cells which stained positive for the collagen also stained positive for the muscle proteins. Taken together, the results suggested that type XIX collagen may be involved in the initial stages of skeletal muscle cell differentiation.
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PMID:Up-regulation of type XIX collagen in rhabdomyosarcoma cells accompanies myogenic differentiation. 1058 82

Type XIX collagen was discovered from the sequence of rhabdomyosarcoma cDNA clones. The chain is composed of a 268-residue amino terminus, an 832-residue discontinuous collagenous region, and a 19-residue carboxyl peptide. Light microscopy immunohistochemistry of adult human tissues demonstrated that type XIX is localized in vascular, neuronal, mesenchymal, and some epithelial basement membrane zones. It also appears to be involved in events linked to skeletal myogenesis. In this report, we have presented the first direct evidence for the molecular structure of type XIX collagen. Using human umbilical cord, native type XIX was purified by neutral salt extraction and by ion exchange and antibody affinity chromatography. Type XIX was found to represent only approximately 10(-6)% of the dry weight of tissue, making it by far the least abundant collagen ever isolated. Transmission electron microscopy after rotary shadowing revealed the appearance of rodlike structures with multiple sharp bends, a small nodule at one end of the molecule, and a total length of 240 nm. Domain-specific antibodies were used to identify the nodule as the noncollagenous amino terminus, whereas the location of most kinks corresponds to major interruptions separating the five collagenous subdomains. More than half of the type XIX molecules observed were present in oligomers of different size and complexity, resulting from association of the amino-terminal domains. Biochemical analysis demonstrated that these supramolecular aggregates are dependent upon and/or stabilized by intermolecular disulfide cross-links and that the globular amino terminus contains a high affinity, heparin-binding site. The polymorphic conformational states of this rare collagen, and its ability to self-assemble into a higher order structure provide focal points for future determination of biologically significant functions in cell-cell and/or cell-matrix interactions.
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PMID:Type XIX collagen purified from human umbilical cord is characterized by multiple sharp kinks delineating collagenous subdomains and by intermolecular aggregates via globular, disulfide-linked, and heparin-binding amino termini. 1278 17