Abstract
Transglutaminases (TGMs) contribute to the formation of rigid, insoluble macromolecular complexes, which are essential for the epidermis and hair follicles to perform protective and barrier functions against the environment. During differentiation, epidermal keratinocytes undergo structural alterations being transformed into cornified cells, which constitute a highly tough outermost layer of the epidermis, the stratum corneum. Similar processes occur during the hardening of the hair follicle and the hair shaft, which is provided by the enzymatic cross-linking of the structural proteins and keratin intermediate filaments. TGM3, also known as epidermal TGM, is one of the pivotal enzymes responsible for the formation of protein polymers in the epidermis and the hair follicle. Numerous studies have shown that TGM3 is extensively involved in epidermal and hair follicle physiology and pathology. However, the roles of TGM3, its substrates, and its importance for the integument system are not fully understood. Here, we summarize the main advances that have recently been achieved in TGM3 analyses in skin and hair follicle biology and also in understanding the functional role of TGM3 in human tumor pathology as well as the reliability of its prognostic clinical usage as a cancer diagnosis biomarker. This review also focuses on human and murine hair follicle abnormalities connected with TGM3 mutations.
Highlights
Many physiologically important protein cross-linking reactions in mammals are orchestrated by transglutaminases (TGMs)
The activity of TGM3 was shown to be directed at the following proteins: SPR2, SPR4 [80], recombinant suprabasin, which is found in the interfollicular epidermis and the companion layer [69], and SPINK 6 expressed by cortex cells of the hair follicle [69]
uncombable hair syndrome (UHS) as the hair phenotype related to alterations in TGM3 and in the other proteins of the trichohyalin-PAD3-TGM3 cascade. They draw the similar conclusion as was made by John et al.: the fact that no anomalies have been reported in the interfollicular epidermis of individuals with isolated UHS as in stratified epithelia of Tgm3−/− mice [86] may be explained by the presence of other isoforms of these enzyme families in the epidermis, which can compensate for the loss of PAD3 and TGM3 activity, whereas these two are the only isoforms detected in the human hair cuticles and medulla [26,73,106]
Summary
Many physiologically important protein cross-linking reactions in mammals are orchestrated by transglutaminases (TGMs). Factor XIII was unequivocally confirmed playremaining a role in thefive fibrin clot stabilization [13], but recent mechanical properties of erythrocytes [15].toThe. TGMs are determined to be of great studies suggest it to be involved in corneal epithelium maintenance and corneal wound healing importance for epidermal and hair follicle morphogenesis (Table 1) playing mainly a structural role and process [14]. TGM2 does not seem to play the central role in the epidermis, it has been recently revealed as a in dermal fibroblasts and contributes to extracellular matrix formation via binding fibronectin and mediator of the epidermal inflammatory response to UV irradiation [18]. TGM5 plays expression is altered in diseases related to abnormal keratinization, such as psoriasis and ichthyosis an important role in keratinocyte differentiation and the cornification of the epidermis, since its [23]. The potential involvement of TGM3 in diverse biological processes makes it a subject of special interest for scientists
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