The type‐1 repeats of thyroglobulin regulate thyroglobulin degradation and T3, T4 release in thyrocytes

Molina, Franck; Pau, Bernard; Granier, Claude

doi:10.1016/0014-5793(96)00708-9

Cited by 29 publications

(20 citation statements)

References 28 publications

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“…self-folding structural units, and can act as proteinase inhibitors in other proteins (Lenarcic & Bevec 1998). It is hypothesized that the type-1 repeats in TG could act as pH-dependent binders and reversible inhibitors of the proteases implicated in TG degradation and T 4 release (Molina et al 1996), but up till now no definite function for this type of repeat in TG has been established. No mutations that could shed more light on the role of the cysteine type-1 repeats in TG have been reported in any of the cysteine residues located in the type-1 domains.…”

Section: Resultsmentioning

confidence: 99%

“…To complete the complex profile of the TG protein, the human acceptor and the donor tyrosine residues (Lamas et al 1989, Dunn 1999, N-glycosylation sites (Yang et al 1996), the cysteineresidue-rich repeated domains (Malthièry & Lissitzky 1987, Gentile & Salvatore 1993, Molina et al 1996, the acetylcholinesterase homologous domain (Swillens et al 1986), the proposed binding domain to the N-acetylglucosamine receptor (Mezgrhani et al 1997), the recently identified thioredoxin boxes (Klein et al 2000), and the most prominent antigenic epitopes (Henry et al 1992, Mallet et al 1992, Kong et al 1995, Saboori et al 1995, Erregragui et al 1997) have been included.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Up to date with human thyroglobulin

Graaf¹,

Ris‐Stalpers²,

Pauws³

et al. 2001

Journal of Endocrinology

137

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The coding region of the human thyroglobulin (TG) mRNA has been resequenced, and comparison with the TG sequence originally published in 1987 showed many variations. All of the variations were validated in 20-40 other alleles, and this resulted in the revision of 41 nucleotide positions. This review presents the revised wild-type human TG sequence, including all known exon/exon boundaries and additional data on the TG mRNA population, concerning alternative splicing and variability of the polyadenylation cleavage site. The amino acid sequence derived shows one additional, 12 changed, and 10 polymorphic residues. Protein characteristics, such as acceptor and donor tyrosine residues, N-glycosylation sites, cysteine-rich repeats, the proposed receptor domain, and antigenic epitopes, are included, and their relationship to the revised sequence is discussed. Furthermore, all reported TG mutations causing dyshormonogenesis in humans and animals are designated in the nucleotide and amino acid sequences. This up-to-date profile of the human TG molecule presents the features of importance for its complex role in thyroid hormonogenesis, and is the basis for future studies on the structure-function relationship.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Up to date with human thyroglobulin

Graaf¹,

Ris‐Stalpers²,

Pauws³

et al. 2001

Journal of Endocrinology

137

View full text Add to dashboard Cite

show abstract

“…Some of these domains show various degrees of homology with numerous proteins (Takagi et al 1991, Molina et al 1996a. This has led to various hypothetical functions (Swillens et al 1986, Molina et al 1996b) being attributed to Tg domains, which are thought to be mediated by Tg interactions with specific ligands. This accounts for the large number of proteins able to bind Tg.…”

Section: Introductionmentioning

confidence: 99%

Identification of thyroglobulin domain(s) involved in cell-surface binding and endocytosis

Siffroi-Fernandez

Delom²,

Nlend³

et al. 2001

Journal of Endocrinology

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Thyroglobulin (Tg) binds to cell surfaces through various binding sites of high, moderate and low affinity. We have previously shown that binding with low to moderate affinity is pH dependent, selective, but not tissue specific. To identify the regions of Tg involved in this cell surface binding, we studied the binding of 125 I-labeled cyanogen bromide peptides from human Tg to cell surfaces of thyroid cells (inside-out follicles) and of CHO cells. Electrophoretic analysis of cell homogenates after binding of native or of reduced and alkylated 125

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“…Tg degradation is a complex process, starting with the solubilization of stored Tg from covalently crosslinked globules by cathepsins B and L, limited digestion by cathepsins K and L for extracellular T4 liberation (in the lumen), and final reentry into endolysosomes for complete proteolysis by several lysosomal enzymes (43). In addition, several proteases may act in concert, and their activities may be influenced by their subcellular location (44) or by protease-resistant segments (type 1 repeats) of Tg itself (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Identification of Pathogenic T Cell Epitopes Near Cathepsin Cleavage Sites in Thyroglobulin

Kolypetri

Jiang

Carayanniotis

2013

The Journal of Immunology

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Experimental autoimmune thyroiditis, induced in mice after challenge with thyroglobulin (Tg), is known to be under the genetic control of the H2Ak locus. Because cathepsins are known to influence proteolytic processing of Tg in vivo, we examined in this study whether putative H2Ak-binding Tg epitopes, located near cathepsin cleavage sites within mouse Tg, have immunopathogenic properties. Cathepsin L, B, and D cleavage sites in mouse Tg were predicted based on homology with known cathepsin cleavage sites in rabbit Tg. We used an algorithm-based approach to identify H2Ak-binding motifs within 20-aa residue segments adjacent to cathepsin cleavage sites, and five 12mer peptides encompassing these sequences were synthesized. Two of them, p2369 (aa 2369–2380) and p2439 (aa 2439–2450) were immunogenic, eliciting significant proliferative T cell responses using lymph node cells from peptide-primed mice and production of IL-2 and IFN-γ in recall assays in vitro. Both peptides induced experimental autoimmune thyroiditis upon direct challenge of CBA/J mice with peptide in CFA and by adoptive transfer of peptide-primed lymph node cells into naive recipient hosts, but neither peptide was characterized as dominant.

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The type‐1 repeats of thyroglobulin regulate thyroglobulin degradation and T3, T4 release in thyrocytes

Cited by 29 publications

References 28 publications

Up to date with human thyroglobulin

Up to date with human thyroglobulin

Identification of thyroglobulin domain(s) involved in cell-surface binding and endocytosis

Identification of Pathogenic T Cell Epitopes Near Cathepsin Cleavage Sites in Thyroglobulin

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