Thyroglobulin, the prothyroid hormone: chemistry, synthesis and degradation

Deshpande, Vijay; Venkatesh, Sriram

doi:10.1016/s0167-4838(99)00015-1

Cited by 26 publications

(24 citation statements)

References 194 publications

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“…BSA (66 kDa), bovine thyroglobulin (669 kDa as a dimer under native conditions (42)(43)(44)(45)), and equine myoglobin (17 kDa) were purchased from Sigma-Aldrich. UCHL-1 and DJ-1 were expressed and purified as described elsewhere (for UCHL-1, see Ref.…”

Section: Methodsmentioning

confidence: 99%

“…We observed only low signal to noise, unresolved signal at 2500 -4000 m/z (data not shown) using electrospray, and no signal using MALDI-TOF (data not shown). Thyroglobulin is not only large in size but is also heterogenous in composition with many PTMs including iodination, glycosylation, and disulfide bonds (44). We performed funnel-skimmer dissociation from two different solvents (Fig.…”

Section: Evaluation Of the Hypothetical Requirements For The Identifimentioning

confidence: 99%

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Sensitive and Specific Identification of Wild Type and Variant Proteins from 8 to 669 kDa Using Top-down Mass Spectrometry

Karabacak

Tiwari

et al. 2009

Molecular & Cellular Proteomics

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Top-down and bottom-up mass spectrometry methods can generate gas phase fragments and use these to identify proteins. Top-down methods, in addition, can provide the mass of the protein itself and therefore additional structural information. Despite the conceptual advantage of top-down methods, the market share advantage belongs to bottom-up methods as a result of their more robust sample preparation, fragmentation, and data processing methods. Here we report improved fragmentation and data processing methods for top-down mass spectrometry. Specifically we report the use of funnel-skimmer dissociation, a variation of nozzle-skimmer dissociation, and compare its performance with electron capture dissociation. We also debut BIG Mascot, an extended version of Mascot with incorporated top-down MS 2 search ability and the first search engine that can perform both bottom-up and top-down searches. Using BIG Mascot, we demonstrated the ability to identify proteins 1) using only intact protein MS Ionization and detection of intact proteins have been possible for 20 years (1, 2). This breakthrough, combined with the development of methods of intact protein fragmentation (3-9) and database searching (10 -12), gave rise to top-down mass spectrometric approaches of protein analysis (13-19). Although top-down proteomics excels in the area of protein variant and post-translational modification (PTM) 1 characterization (14, 20, 21), comprehensive protein identification is an area for improvement (22-24). Top-down proteomics is hampered by the lack of a sample preparation technique as generally applicable as in-gel digestion (25), the lack of a fragmentation technique as robust as collisionally activated dissociation (CAD) of peptides (26), and the lack of compatibility of top-down MS data with all popular bottom-up software (27), including Mascot (28), Sequest (29), Protein Prospector (30), and Peptide Search (31). Recent improvements in these areas include the following: 1) separation techniques compatible with top-down analysis (18, 32); 2) fragmentation techniques, including nozzle-skimmer dissociation (3, 33-35), electron transfer dissociation (7, 8), prefolding dissociation (9), and activated ion electron capture dissociation (ECD) (5), which extended the protein upper mass limit to 229 kDa for top-down methods (9); and 3) a search engine as advanced as any bottom-up software; ProSight PTM (11, 12, 36) was developed and integrated with a comprehensive MS database within the Xcalibur software suite (Thermo Finnigan, San José , CA). Our objectives here are (i) to help develop an extended version of Mascot that incorporates top-down MS 2 search ability and (ii) to infer its search sensitivity and selectivity. Here we present BIG Mascot, the first general use search engine that can perform both bottom-up and top-down MS 2 searches. Mascot has been one of the most widely used database search engines because of its probability-based scoring method (28), its superior performance (37, 38), and its fast operating algorithm. However,...

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Section: Methodsmentioning

confidence: 99%

Section: Evaluation Of the Hypothetical Requirements For The Identifimentioning

confidence: 99%

Sensitive and Specific Identification of Wild Type and Variant Proteins from 8 to 669 kDa Using Top-down Mass Spectrometry

Karabacak

Tiwari

et al. 2009

Molecular & Cellular Proteomics

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“…Both T 4 and T 3 formation involve a coupling reaction between an acceptor di-iodotyrosine (DIT), which becomes the site of hormone formation within TG (8), and a donor iodotyrosine [either DIT or mono-iodotyrosine (MIT) for T 4 and T 3 formation, respectively] that is converted into dehydroalanine or pyruvate (9). There is good evidence suggesting that much of the T 4 formation involves intra-monomer coupling between the Tyr5 acceptor and a Tyr130 donor (10,11); however, the MIT donor responsible for T 3 formation at the antepenultimate residue (i.e., the third-to-last residue of TG falling within the sequence SYSK) has remained unclear.…”

Section: Introductionmentioning

confidence: 99%

Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine

Citterio

Morishita

Dakka

et al. 2018

Journal of Biological Chemistry

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“…Thyroglobulin, the major secretory product of the thyroid, is the protein precursor for thyroid hormones. It is a 330-kDa glycoprotein that undergoes homodimerization in the endoplasmic reticulum and other posttranslational modifications (i.e., phosphorylation, N-and O-glycosylation, sulfation, and iodination) (13). Thyroglobulin mRNA production is regulated by TSH, as well as by insulin and insulin-like growth factor I (45).…”

mentioning

confidence: 99%

Pendrin Is a Novel In Vivo Downstream Target Gene of the TTF-1/Nkx-2.1 Homeodomain Transcription Factor in Differentiated Thyroid Cells

Dentice¹,

Luongo

Elefante

et al. 2005

Molecular and Cellular Biology

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Thyroid transcription factor gene 1 (TTF-1) is a homeobox-containing gene involved in thyroid organogenesis. During early thyroid development, the homeobox gene Nkx-2.5 is expressed in thyroid precursor cells coincident with the appearance of TTF-1. The aim of this study was to investigate the molecular mechanisms underlying thyroid-specific gene expression. We show that the Nkx-2.5 C terminus interacts with the TTF-1 homeodomain and, moreover, that the expression of a dominant-negative Nkx-2.5 isoform (N188K) in thyroid cells reduces TTF-1-driven transcription by titrating TTF-1 away from its target DNA. This process reduced the expression of several thyroid-specific genes, including pendrin and thyroglobulin. Similarly, down-regulation of TTF-1 by RNA interference reduced the expression of both genes, whose promoters are sensitive to and directly associate with TTF-1 in the chromatin context. In conclusion, we demonstrate that pendrin and thyroglobulin are downstream targets in vivo of TTF-1, whose action is a prime factor in controlling thyroid differentiation in vivo.

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Thyroglobulin, the prothyroid hormone: chemistry, synthesis and degradation

Cited by 26 publications

References 194 publications

Sensitive and Specific Identification of Wild Type and Variant Proteins from 8 to 669 kDa Using Top-down Mass Spectrometry

Sensitive and Specific Identification of Wild Type and Variant Proteins from 8 to 669 kDa Using Top-down Mass Spectrometry

Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine

Pendrin Is a Novel In Vivo Downstream Target Gene of the TTF-1/Nkx-2.1 Homeodomain Transcription Factor in Differentiated Thyroid Cells

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