Inhibition of procollagen cell-free synthesis by amino-terminal extension peptides

Paglia, Larry; Wilczek, Joseph; León, Lino Díaz de; Martin, George R.; Hoerlein, Dietrich; Mueller, Peter

doi:10.1021/bi00589a034

Cited by 115 publications

(54 citation statements)

References 27 publications

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“…Support for such a function was provided initially by the observation that isolated N-propeptide, produced from dermatosparactic calf skin collagen by bacterial collagenase digestion, reduced collagen synthesis by bovine fibroblasts in culture and that dermatosparactic bovine fibroblasts, which are deficient in PNP activity, synthesized more collagen in culture than control cells (18,36). Subsequently, it was shown that bovine N-propeptide was capable of selectively inhibiting the translation of collagenenriched mRNA in cell-free reticulocyte lysate systems (19,20), whereas chick N-propeptide reduced procollagen mRNA levels in human fibroblasts (37). More recently, Fouser et al (21) transfected a metallothionein-human N-propeptide minigene into fetal calf ligament cells and observed a selective reduction in type I collagen synthesis in these cells.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with a feedback inhibitory effect, a bacterial collagenase-resistant fragment of the N-propeptide reduced collagen synthesis when it was added to bovine or human fibroblasts (18). Subsequently, it was shown that this collagenase-resistant peptide specifically inhibited the translation of types I and III mRNA in a cell-free translation system (19,20) and that the transfection of bovine nuchal ligament cells with a plasmid encoding the Npropeptide selectively reduced endogenous collagen synthesis by these cells (21). The mechanisms responsible for these effects are still not understood.…”

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confidence: 99%

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The Globular Domain of the Proα1(I) N-Propeptide Is Not Required for Secretion, Processing by Procollagen N-Proteinase, or Fibrillogenesis of Type I Collagen in Mice

Börnstein

Walsh

Tullis

et al. 2002

Journal of Biological Chemistry

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The globular domain in the NH 2 -terminal propeptide (N-propeptide) of the pro␣1(I) chain is largely encoded by exon 2 of the Col1a1 gene and has been implicated in a number of processes that are involved in the biogenesis, maturation, and function of type I collagen. These include intracellular chain association, transcellular transport and secretion, proteolytic processing of the precursor, feedback regulation of synthesis, and control of fibrillogenesis. However, none of these proposed functions has been firmly established. To evaluate the function of this procollagen domain we have used a targeted mutagenesis approach to generate mice that lack exon 2 in the Col1a1 gene. Mouse lines were established on both a mixed 129 OlaHsd/Sv and C57BL/6 background and a pure 129 OlaHsd/Sv background. Adult mice on the mixed background are normal in appearance and are fertile. To the extent that they have been studied, procollagen synthesis, secretion, and proteolytic processing are normal in these mice, and collagen fibrillogenesis is only slightly altered. However, breeding of heterozygous mutant mice on the 129 background generated homozygous mutants at only 64% of the expected frequency. These findings suggest that although the Npropeptide is not essential for collagen biogenesis in mice it may play some essential role during embryonic development.Type I collagen is synthesized as a precursor, procollagen, with NH 2 -and COOH-terminal non-triple helical extensions (N-and C-propeptides) that are released extracellularly by limited proteolysis with procollagen N-and C-proteinases (1-4). The C-propeptide domain of procollagen participates in the association of the two pro␣1 and one pro␣2 chains to initiate triple helix formation from the COOH terminus of the protein (5-7).A number of functions have been proposed for the ␣1(I) N-propeptide in the biogenesis of type I collagen, including prevention of premature intracellular molecular association and facilitation of transcellular transport and secretion, conversion of procollagen to collagen, regulation of extracellular fibrillogenesis, and feedback regulation of procollagen synthesis. However, none of these functions has been established unequivocally, and some have been questioned. Lee et al. (8) studied the secretion of mutated type I procollagen, generated from human cDNA genes that were transfected into Chinese hamster lung, Mov-13, and COS-7 cells. Whereas wild-type (WT) 1 procollagen was secreted efficiently, proteins lacking either the entire N-propeptide (139 amino acids) or the majority of it (114 amino acids) were secreted poorly from Chinese hamster lung cells. In contrast, the WT and mutant proteins were secreted equally well by Mov-13 and COS-7 cells. Because Chinese hamster lung cells are epithelial-like, whereas Mov-13 and COS-7 cells are fibroblast-like, the failure of the former to secrete a collagen lacking N-propeptides may be unrelated to the structure of the protein. In all cases, triple helical assembly of the transfected gene products occurred nor...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Globular Domain of the Proα1(I) N-Propeptide Is Not Required for Secretion, Processing by Procollagen N-Proteinase, or Fibrillogenesis of Type I Collagen in Mice

Börnstein

Walsh

Tullis

et al. 2002

Journal of Biological Chemistry

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“…The aminopropeptide is thought to inhibit collagen synthesis in vivo [9,10]. If a similar mechanism operates in cell culture the antibody should increase collagen synthesis when added to the culture by lowering the amount of endogenous peptide.…”

Section: Discussionmentioning

confidence: 99%

A Monoclonal Antibody Specific for the Amino Terminal Cleavage Site of Procollagen Type I

Foellmer

Kawahara

Madri

et al. 1983

European Journal of Biochemistry

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A monoclonal mouse IgGl antibody was produced against the aminopropeptide of dermatosparactic sheep procollagen type I by using the hybridoma technique. Radioimmunoassays demonstrated an apparent affinity constant of lo8 1 . m o l~ '. The antibody reacted with a 19-amino-acid-long sequence spanning the procollagen N-proteinase cleavage site with stronger binding to structures contributed by the aminopropeptide. The antibody showed strong cross-reactions with similar antigens of bovine, human or chick origin but failed to react with the aminopropeptide of procollagen type 111. Incubation of chick or sheep procollagen type I with stoichiometric amounts of antibody blocked the release from procollagen molecules of the aminopropeptide by procollagen N-proteinase. Thus, this antibody seems useful for studying various biological problems encountered in the conversion of procollagen.Aminopropeptides are precursor-specific segments located at the aminoterminal end of interstitial procollagens [I, 21, which are released by a specific procollagen N-proteinase [3 -51 during the conversion of procollagen to collagen. A convenient source of the aminopropeptide is pNcollagen type I from dermatosparactic animals, which has allowed the complete elucidation of the amino acid sequence of the peptide [6,7]. The structural analyses identified three distinct domains in the peptide [6-81. Two non-collagenous fragments can be released from the aminopropeptide by collagenase treatment. They correspond to a compact, disulfide-bonded domain located at its amino end (fragment Coll) and a short nonhelical segment at its carboxyl end (fragment C012) containing the cleavage site for procollagen N-proteinase. Both fragments are joined to each other in the intact aminopropeptide by a short triple-helical segment.Several biological functions have been suggested for the aminopropeptide. It may control collagen synthesis by feedback inhibition as demonstrated with cultured cells [9] and in cell-free translation [lo]. In addition, the liberation of the peptide from procollagen may also regulate collagen fibrillogenesis in tissues [I I].Polyclonal rabbit antibodies against the aminopropeptide have been useful tools in previous studies on its structure and tissue distribution [I 1 -151. These antibodies predominantly react with the Coll segment of the peptide. Antibodies with similar specificity have been described in mice and appear to be regulated by immune-response genes [16,17]. Since the release of the aminopropeptide from the intact procollagen precursor molecule may play a role in several biological phenomena we have produced monoclonal antibodies [I 81, which may provide useful probes with which to study these Dedicated to the 60th anniversary of Prof. E. Buddecke. Ahhrrviufiom. We use the term procollagen for the intact precursor containing both the aminopropeptide and carboxypropeptide. pC collagen and pNcollagen refer to intermediate forms, which have lost either the aminopropeptide (pC) or the carboxypropeptide (pN).events. Here, we rep...

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“…It has been shown, using rat calvaria RNA in a reticulocyte cell-free translation system, that amino-terminal peptides of a1(I) and a1(III) procollagen chains inhibit the production of a1(I) and a2(I) procollagen chains. 30) Recently, SPARC (secreted protein acidic and rich in cysteine), a matricellular glycoprotein (also known as BM-40, osteonectin, or 43-kDa protein) has been shown to regulate the expression of collagen I via activation of the TGF-b signalling pathway in mouse mesangial cells. 31) Further studies will focus on the identiˆcation of the signaling pathway in SaM-1 cells activated by collagen VI andˆnding if its up-regulation of collagen I gene expression involves direct or indirect signalling.…”

Section: )mentioning

confidence: 99%

Antisense Suppression of Collagen VI Synthesis Results in Reduced Expression of Collagen I in Normal Human Osteoblast-like Cells

Harumiya¹,

Gibson²,

Koshihara³

2002

Bioscience, Biotechnology, and Biochemistry

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Inhibition of procollagen cell-free synthesis by amino-terminal extension peptides

Cited by 115 publications

References 27 publications

The Globular Domain of the Proα1(I) N-Propeptide Is Not Required for Secretion, Processing by Procollagen N-Proteinase, or Fibrillogenesis of Type I Collagen in Mice

The Globular Domain of the Proα1(I) N-Propeptide Is Not Required for Secretion, Processing by Procollagen N-Proteinase, or Fibrillogenesis of Type I Collagen in Mice

A Monoclonal Antibody Specific for the Amino Terminal Cleavage Site of Procollagen Type I

Antisense Suppression of Collagen VI Synthesis Results in Reduced Expression of Collagen I in Normal Human Osteoblast-like Cells

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