Transglutaminase 5 is regulated by guanine–adenine nucleotides

Candi, Eleonora; Paradisi, Andrea; Terrinoni, Alessandro; Pietroni, Valentina; Oddi, Sergio; Cadot, Bruno; Jogini, Vishwanath; Meiyappan, Muthuraman; Clardy, Jon; Finazzi‐Agrò, Alessandro; Melino, Gerry

doi:10.1042/bj20031474

Cited by 52 publications

(46 citation statements)

References 21 publications

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“…However, when we examined the endogenous pool of PS-R in wild-type versus TG-2 (-/-) MEFs, there was no apparent reduction in PS-R covalent modification as assessed by Western blotting (Fig 3A). Further, to rule out the possibility that other ubiquitous family members, such as TG-5 or TG-6, [25] may compensate for TG-2, we made a mutation to disrupt the conserved QQ duet that makes up the TG consensus sequence (Fig. 3B).…”

Section: Resultsmentioning

confidence: 99%

Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product

Tibrewal

Liu

et al. 2007

Mol Cell Biochem

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The PS-R gene product was originally described as a cell surface receptor that interacts with externalized phosphatidylserine (PS) on apoptotic cells, but more recent studies have shown that it plays a critical role in organ development and terminal differentiation of many cell types during embryogenesis. Despite these important developmental functions, the biochemical and molecular properties of PS-R are poorly understood. Here we have used several approaches to show that PS-R undergoes processive post-translational protein cross-linking to form covalent multimers within the nuclear compartment. Although PS-R has a potential Glu-Glu (QQ) duet that is often targeted by transglutaminase TG-2, the oligomerization of PS-R was not effected by QQ fi AA mutation, or when PS-R gene product was expressed in TG-2 (-/-) fibroblasts. Pulse-chase experiments with 35 S-methionine indicates that the PS-R undergoes an initial proteolytic cleavage, followed by progressive multimerization of the monomeric subunits over time. In summary, we report here that PS-R is modified by an unusual post-translational modification, and we speculate that homomultimer of PS-R might be playing an important function as a scaffolding protein in the nucleus.

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Section: Resultsmentioning

confidence: 99%

Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product

Tibrewal

Liu

et al. 2007

Mol Cell Biochem

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“…TG5 appears to associate with the vimentin intermediate filament network in cultured keratinocytes that are undergoing epithelialmesenchymal transition (53). TG5 is also found in several fetal and adult tissues; however, the exact cell type that expresses this protein in these tissues is not yet known (54). A loss-of-function mutation in TGM5 has been reported to cause acral peeling skin syndrome (57).…”

Section: Tg5mentioning

confidence: 99%

“…GDP and the reactive gluten-peptide mimic inhibitor Ac-P(DON)LPF-NH 2 are shown as black lines. Although only TG2 (38,118,121,122), TG4 (262), and TG5 (54) have been shown to bind GTP, the crystal structures of all human TGs solved in the absence of calcium [FXIII-A (305), TG2 (37,162), TG3 (11)] assume the same compact conformation, in which the TG active site is buried. B: dotted lines indicate exons encoding structural domains of the protein, with the relative location of the transition-state-stabilizing Trp, and active site Cys, His, and Asp shown.…”

Section: General Introductionmentioning

confidence: 99%

Transglutaminases and Disease: Lessons From Genetically Engineered Mouse Models and Inherited Disorders

Iismaa¹,

Mearns²,

Lóránd³

et al. 2009

Physiological Reviews

305

336

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The human transglutaminase (TG) family consists of a structural protein, protein 4.2, that lacks catalytic activity, and eight zymogens/enzymes, designated factor XIII-A (FXIII-A) and TG1-7, that catalyze three types of posttranslational modification reactions: transamidation, esterification, and hydrolysis. These reactions are essential for biological processes such as blood coagulation, skin barrier formation, and extracellular matrix assembly but can also contribute to the pathophysiology of various inflammatory, autoimmune, and degenerative conditions. Some members of the TG family, for example, TG2, can participate in biological processes through actions unrelated to transamidase catalytic activity. We present here a comprehensive review of recent insights into the physiology and pathophysiology of TG family members that have come from studies of genetically engineered mouse models and/or inherited disorders. The review focuses on FXIII-A, TG1, TG2, TG5, and protein 4.2, as mice deficient in TG3, TG4, TG6, or TG7 have not yet been reported, nor have mutations in these proteins been linked to human disease.

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“…4 for references therein). Four of the nine human TGs (TG1-3 and -5) are expressed in the brain (5,6). The most investigated TG2 is present in two splice variants, the shorter of which results from an intronic read-through and was shown to associate with Alzheimer neurons (7).…”

Section: And References Therein)mentioning

confidence: 99%

Transglutaminase-mediated Intramolecular Cross-linking of Membrane-bound α-Synuclein Promotes Amyloid Formation in Lewy Bodies

Nemes

Petrovski

Aerts

et al. 2009

Journal of Biological Chemistry

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The ␣-synuclein immunopositive and chaotrope-insoluble material from human brains with Lewy body pathology was analyzed by mass spectrometry. From the proteinase K-cleavable peripheral fraction of Lewy bodies, which was densely crosslinked by ␥-glutamyl-⑀-lysine bonds between HspB1 and ubiquitin in a pattern similar to neurofibrillary tangles (Nemes, Z., Devreese, B., Steinert, P. M., Van Beeumen, J., and Fésüs, L. (2004) FASEB J. 18, 1135-1137), 53 proteins were identified. In the core of Lewy bodies only ␣-synuclein was found, and it contained a low amount of intramolecular cross-links between Gln-99 and Lys-58. In vitro cross-linking of ␣-synuclein by transglutaminases 1-3 and 5 produced a heterogeneous population of variably cross-linked ␣-synucleins in solution, which inhibited the aggregation of the protein into amyloid. However, in the presence of phosphatidylserine-rich membranes and micromolar calcium concentrations, the cross-linking by transglutaminases 1, 2, and 5 showed specificity toward the utilization of Gln-99 and Lys-58. As shown by thioflavin T fluorescence monitoring, the formation of this cross-link accelerated the aggregation of native ␣-synuclein. Chemical cross-linking of residues 58 -99 triggered amyloid formation, whereas such bonding of residues 99 to 10 was inhibitory. Our findings reveal the pivotal role of membrane attachment and transglutaminasemediated intermolecular cross-linking for the propagative misfolding and aggregation of ␣-synuclein.

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Transglutaminase 5 is regulated by guanine–adenine nucleotides

Cited by 52 publications

References 21 publications

Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product

Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product

Transglutaminases and Disease: Lessons From Genetically Engineered Mouse Models and Inherited Disorders

Transglutaminase-mediated Intramolecular Cross-linking of Membrane-bound α-Synuclein Promotes Amyloid Formation in Lewy Bodies

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