Disease relevance of TGM3

• Functional studies of a novel oncogene TGM3 in human esophageal squamous cell carcinoma [1]
• Expression of TGM3 was significantly inversely correlated with histological grade of esophageal carcinoma (in grade I, II and III tumors, the reduced expression was 4/7, 57/71, and 20/21, respectively, P < 0.05), whereas it had no obvious correlations with lymph node metastasis and depth of invasion [1]
• METHODS: Gene expression of TGM3 in fresh esophageal cancer tissues and their corresponding normal mucosas was detected immunohistochemically (IHC) by means of tissue microarray (TMA) [1]
• In Darier's disease, transglutaminase 5 expression, as well as transglutaminase 3, is completely missregulated, being overexpressed or totally absent in different areas of the same lesion [2]
• No degradation of CLSP in psoriatic epidermis keeping its ability to bind protein as transglutaminase 3 may have a physiological role in skin diseases such as psoriasis [3]

High impact information on TGM3

• Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calcium/magnesium [4]
• Sequencing of a rCLSP affinity purified protein revealed 100% identity with transglutaminase 3, a key enzyme in terminal differentiation, indicating an important role of CLSP in this process [5]
• As these TGM3 sequences can confer promoter/enhancer activity to reporter genes at a level comparable to the powerful SV40 promoter, they may be useful for gene therapy in keratinocytes [6]
• Deletion analyses in transiently transfected epidermal keratinocytes defined sequences between -126 and -91 as the proximal promoter region of the gene, and which can confer epithelial-specific expression to the TGM3 gene in vitro [6]
• To explore the mechanisms regulating the expression of the transglutaminase 3 gene (TGM3), 3.0 kilobase pairs of sequences upstream from the transcription start site were assessed for their ability to control the expression of a chloramphenicol acetyltransferase reporter gene [6]

Biological context of TGM3

• In the course of isolation of genomic clones for the TGM3 gene, we also found clones encoding the widely expressed tissue or TGase2 enzyme, perhaps due to high degrees of sequence homology [7]
• In this paper we show that it is encoded by a gene (TGM3) of 42.8 kbp containing 13 exons [7]
• Assignment of the human transglutaminase 2 (TGM2) and transglutaminase 3 (TGM3) genes to chromosome 20q11.2 [8]
• Strongly negative lod scores prompted a search for linkage to two other epidermally expressed transglutaminases, transglutaminase-2 and transglutaminase-3, on chromosome 20 [9]
• Two of the three heat shock proteins were identified by mass spectrometric sequencing to be the calcium-calmodulin homologue transglutaminase-3 (78 kDa) and a recently cloned oesophageal-specific gene called C1orf10, which encodes a 53-kDa putative calcium binding protein we have named squamous epithelial heat shock protein 53 (SEP53) [10]

Anatomical context of TGM3

• Other areas, particularly those showing non-keratinizing epithelium, showed weak immunostaining of TGase E and C, suggesting its different maturation status from keratinizing epithelium [11]
• The transglutaminase 3 enzyme is expressed during the late stages of the terminal differentiation of the epidermis and in certain cell types of the hair follicle [6]
• The proximal promoter of the human transglutaminase 3 gene. Stratified squamous epithelial-specific expression in cultured cells is mediated by binding of Sp1 and ets transcription factors to a proximal promoter element [6]
• RT-PCR demonstrated the presence of significant mRNA amounts of transglutaminase 2 and transglutaminase 1, both in the hippocampus and the cerebral cortex, while low levels were found for transglutaminase 3 transcripts [12]
• Clonal heterogeneity of the sensitivity of human colon carcinoma cell lines to TGE beta isoforms [13]

Associations of TGM3 with chemical compounds

• Transglutaminase-3 (TGase-3) is an enzyme with the ability to catalyze the irreversible cross-linking of peptide-bound glutamine residues either with peptide-bound lysines or with primary amines [14]
• Transglutaminase-3 (TGM3) can modify different proteins, like small proline rich proteins 1-3, invlucrin, loricrin, huntingtins etc. serving as glutamyl or lysyl donors in the crosslinking reactions. A list of identified substrates is included in TRANSDAB   database [15]
• Complete cleavage of DNA was observed by complexes containing TGE and ME at 400-600 moles excess of thiol ligand to hemin, those containing Cys, CysMe, and CysEt at 50-200 moles excess, and those containing MPG, GSH, penta- and nona-peptides at 5-20 moles excess [16]
• Mutation of the critical aspartic acid residue in the phosphorylation domain (DKTGTIT) blocked copper-induced redistribution of ATP7B from the TGN, whereas mutation of the phosphatase domain [TGE (Thr-Gly-Glu)] trapped ATP7B at cytosolic vesicular compartments [17]

Other interactions of TGM3

• Structure and organization of the human transglutaminase 3 gene: evolutionary relationship to the transglutaminase family [7]
• Based on sequence homologies and gene structures, the data support a phylogenic tree in which the TGM2 and TGM3 genes belong on a branch distinct from other transglutaminases [7]
• Differential expression of the keratin-4, -13, -14, -17 and transglutaminase 3 genes during the development of oral squamous cell carcinoma from leukoplakia [18]
• Significantly higher levels of keratin (Ker)-14 and -17 mRNAs, combined with lower levels of Ker-4, Ker-13 and transglutaminase 3 (TG-3) transcripts, were observed in OSCC and severely dysplastic tissues, whereas this expression profile was reversed in hyperplasia and in mild to moderate dysplasia [18]
• BCSG-1 is increased in breast tumour cells, is negatively associated with tumour grade and significantly correlates with levels of transglutaminase-3 [19]

Analytical, diagnostic and therapeutic context of TGM3

• By electrophoretic mobility shift assay (EMSA), the core motif of Ets-binding sequence of TGM3 was determined as ACAGGAAT (-118 to -111 bp from transcriptional start site) [20]
• We found evidence of E1--E4 cross-linking by endogenous transglutaminases in an in situ assay using frozen sections of human foreskin, and in addition, E1--E4 protein was cross-linked by recombinant transglutaminase 3 (but not transglutaminase 1) in an in vitro cross-linking assay [21]
• Crystallization and preliminary X-ray analysis of human transglutaminase 3 from zymogen to active form [22]
• SSFP gave a larger difference for end diastolic volume measurement compared to SPECT than did TGE, although this difference did not reach significance [23]
• In plaque neutralization tests, a slight reduction was observed against TGE and CCV but not against FIP [24]

References