ARTICLE
Auteur(s) : Kiyotaka Hitomi
Department of Applied Molecular Biosciences, Graduate School of
Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya,
464-8601, Japan
accepté le 28 Avril 2005
Transglutaminase introduces covalent cross-linking between
proteins
Skin epidermis functions to form and maintain a protective barrier
against physical, chemical, and microbial damage from the external
environment. The cornified cell envelope (CE), which is formed in
the outermost layer of the epidermis, plays an essential role
because it provides a highly durable and flexible structure as a
barrier [1-5]. The CE contains an insoluble mixture of structural
proteins, including involucrin, loricrin, small proline-rich
proteins (SPRs), envoplakin, periplakin, and various other
proteins. These constituting proteins are covalently cross-linked
to form stable high-molecular-weight components that attach to the
membrane lipid, contributing to protection against trauma,
ultraviolet irradiation, and infections.
Transglutaminases (TGase: 2.3.2.13) are enzymes responsible for
cross-linking between proteins. TGases catalyze the transamidation
of selected peptide-bound glutamine residues in a calcium
dependent-manner ( (figure 1) ). This reaction
causes either the formation of covalent isopeptide bonds within or
between polypeptides or incorporation of primary amines into
substrate proteins. By this cross-linking reaction and
modification, supramolecular structures with extra stability and
novel functions are produced [6, 7]. In humans, eight isozymes that
are involved in various important physiological processes,
including apoptosis, blood coagulation and extracellular matrix
assembly, have so far been identified (table 1)( Table 1 ).
Among the eight isozymes identified in humans, TGases 1, 3, and
5 are mainly expressed in the skin epidermis. It is essential that
these TGases are appropriately regulated and cooperated to
construct the CE during keratinocyte differentiation [8]. TGase 2,
ubiquitously expressed, is located in the epidermal keratinocytes
and also in the dermis. No information on involvement in CE
formation, however, has been reported. Cross-linking by TGase 2
enhances the stability of the extracellular matrix and contributes
to fibroblast wound healing responses [9].
In this review, the expression, regulation of enzymatic activity
and functions of TGases are summarized, with a focus on the
involvement of TGases in the formation of the CE in the skin
epidermis.
Table 1 Human transglutaminase family. Factor XIII,
which is converted by a thrombin-dependent proteolysis into the
active form, is essential for stabilization of fibrin clots and in
wound healing. TGase 2, ubiquitously expressed, is involved in a
variety of cellular process from apoptosis to extracellular matrix
formation. TGases 1, 3 and 5 are expressed in the skin epidermis
and participate in CE formation. The physiological significance of
TGases 6 and 7 remains unknown. Band 4.2, a major membrane skeletal
protein in erythrocyte, is TGase-like molecule that is
catalytically inactive
|
Names
|
kDa
|
Tissue expression
|
Function
|
Gene map locus
|
|
Factor XIII
|
83
|
Plasma, monocyte
|
Blood coagulation
|
6p24-25
|
|
TGase 1
|
106
|
Epithelia, Brain
|
CE formation
|
14q11.2
|
|
TGase 2
|
80
|
Ubiquitous
|
Multiple
|
20q11-12
|
|
TGase 3
|
77
|
Epidermis, hair follicle
|
CE formation
|
20q11-12
|
|
TGase 4
|
77
|
Prostate
|
Semen coagulation (rodents)
|
3p21-22
|
|
TGase 5
|
81
|
Ubiquitous except for brain
|
CE formation
|
15q15.2
|
|
TGase 6
|
80 ?
|
?
|
?
|
20q11
|
|
TGase 7
|
80 ?
|
Ubiquitous
|
?
|
15q15.2
|
|
Band 4.2
|
72
|
Erythrocyte
|
Membrane skeletal component
|
15q15.2
|
TGases 1, 3 and 5 in the skin epidermis
TGase 1
TGase 1 is synthesized as an 817-residue polypeptide, resulting in
a molecular size of approximately 106 kDa. In differentiating
keratinocytes, TGase 1 shows low specific activity as the zymogen
form. During terminal differentiation, TGase 1 is proteolyzed into
a processed form of 10, 33, and 67 kDa complex that are held
together with noncovalent binding [10]. The resulting 10/33/67 kDa
complex shows a drastic enhancement of specific activity and is
responsible for most of TGase 1 activity.
The protease(s) required for activating the zymogen of TGase 1
in vivo remains unknown. Recently, calpain, an intracellular
calcium-dependent protease, and cathepsin D, a lysosomal protease,
have been shown to be candidates for the proteolysis. Using
cultured keratinocytes, Kim et al. showed that a calpain inhibitor
reduces CE formation by inhibiting the processing for TGase 1
activation [11]. Cathepsin D knockout mice show impaired morphology
of the stratum corneum and a phenotype which is similar to that of
lamellar ichthyosis (LI), a TGase 1-related human disease [12]. In
a skin extract of the mouse, both TGase 1 activity and processing
are reduced. These results suggest that a cathepsin D is a
candidate for activating protease of TGase 1.
Results of immunohistological and immunochemical analyses
suggest that TGase 1 is mainly expressed in the granular layer
[13]. Its expression at a later stage of differentiation has also
been confirmed using cultured keratinocytes [14]. Recently, using
specific antibodies recognizing the exposed N-terminal cleavage
site of each fragment, the activated TGase 1 was found to be
located not only in the granular layer but also in the suprabasal
and spinous layers [15]. At the cellular level, most TGase 1 is
attached to the plasma membrane even after proteolysis by
S-myristoylation or palmitoylation at the N-terminus [16].
At the cellular membrane of differentiating keratinocytes, TGase
1 cross-links various structural proteins for CE formation.
Additionally, TGase 1 also contributes to the formation of a
lipid-bound envelope by esterification (cross-linking) of long
chain ω-hydoxyceramides onto CE proteins, mainly involucrin
[17].
Mice lacking TGase 1 show a phenotype with aberrant CE
formation. They have erythrodermic skin with abnormal
keratinization and die within 4-5 hrs after birth due to
dehydration [18]. TGases 3 and 5 cannot compensate for the
cross-linking performed by the absence of TGase 1 in the mice,
indicating that the functions of these TGases are different.
TGase 3
TGase 3 is synthesized as an inactive zymogen form at the molecular
size of 77 kDa that is cleaved into two fragments of 30 kDa and 47
kDa during keratinocyte differentiation [19, 20]. The proteolyzed
fragments, as an active form, are held together noncovalently as in
the case of TGase 1. Upon proteolysis, TGase 3 can acquire
Ca2+ necessary for substrate access [21].
The protease activating of TGase 3 in vivo still remains
elusive. Dispase, a bacterial protease, has been the only known
protease to release fragments of 47 and 30 kDa as the active enzyme
in vitro. Calpain, a possible protease activating for TGase 1,
cannot proteolyze recombinant TGase 3 [22]. A recent study,
however, shows that both cathepsins L and S are able to proteolyze
zymogen form resulting in proteolytic activation in vitro ([5, 23],
Hitomi et al., unpublished data).
TGase 3 is expressed in the brain, small intestine and the
testis, as well as the skin, mainly as a zymogen form [24]. In the
skin, TGase 3 is expressed in the cells of the granular and
cornified layers of the epidermis [25]. In cultured keratinocytes,
TGase 3 displays a diffuse cytoplasmic distribution. Activated
TGase 3 cross-links several structural proteins such as loricrin
and SPRs located in the cytoplasm of keratinocytes.
Different cellular localization of TGase 3 from that of TGase 1
is quite significant in that each TGase has favorable substrates.
For example, TGase 3 favors certain lysines and glutamines of
recombinant loricrin by forming mostly intramolecular cross-links,
whereas TGase 1 forms mostly large oligomeric complexes by
intermolecular reaction [26]. Additionally, recombinant SPR1, one
of the SPRs, is cross-linked sequentially by the TGase 3 followed
by the TGase 1 to form large oligomers [27]. These observations
suggest that TGases 1 and 3 operate in a sequential manner using
different lysine and glutamine residues for cross-linking at the
different cellular sites.
TGase 5
TGase 5 cDNA encodes a protein with 720 amino acids and a molecular
mass of 81 kDa [28]. Unlike TGases 1 and 3, TGase 5 does not
require proteolytic processing for activation [29]. The kinetic and
in vitro cross-linking analyses suggest the full-length TGase 5 is
enzymatically active and use the main epidermal substrates such as
loricrin, involucrin and SPR.
TGase 5 is located mainly in the granular layer of the epidermis
and is also expressed in cultured keratinocytes [30]. In the
keratinocytes stimulated by differentiating agents such as
Ca2+ and the phorbol ester TPA, the level of TGase 5
mRNA is up-regulated transiently.
These biological data suggest that TGase 5 also plays an
important role in the CE formation even though its expression
pattern is not restricted to the skin epidermis (table 1).
Regulators of TGase activity
Various intracellular regulators for TGase activities have been
reported by in vitro analyses: (i) GTP, which is an inhibitor of
TGase 2, also has inhibitory activity toward TGases 3 and 5 in
vitro. The inhibitory effect is reversed by the presence of calcium
ions [22, 31]. (ii) Nitric oxide (NO), a short-lived radical, is
implicated in the inflammatory process, UV-induced melanogenesis
and wound healing in the skin. NO-releasing compounds inhibit the
CE formation in cultured keratinocytes. Results of in vitro
analyses have shown that enzymatic activities of both TGases 1 and
3 are inhibited depending on the NO-donor concentration [32]. This
inhibition is probably due to chemical modification of a cysteine
residue as an active site of TGase, possibly through
S-nitrosylation. (iii) Sphingosylphosphorylcholine (SPC), a
sphingolipid from sphingomyelin, has various biological effects in
keratinocytes [33]. SPC significantly increases TGase activity by
increasing TGase 1 mRNA level. Interestingly, SPC also
concomitantly activates cathepsin D, which is a candidate of the
activating protease for TGase 1. (iv) TIG3, a novel member of the
tumor suppressor protein family (H-rev family), is expressed in the
suprabasal epidermal layers and localized at the cell membrane
[34]. In cultured keratinocytes, over-expression of TIG3 is
associated with increased TGase 1 activity. The enzymatic activity
is enhanced without changing its mRNA and protein level, probably
by interaction with TIG3 [8]. (v) Cholesterol sulfate (CS) is a
membrane lipid formed during the keratinocyte differentiation by
the action of cholesterol sulfotransferase. Treatment of cultured
keratinocyte with CS induced elevation of TGase 1 expression at the
transcriptional level [35]. At a supraphysiological concentration
of CS, conversely, cross-linking reaction as well as ester linkages
of ceramides by TGase 1 is inhibited [36]. In this condition, TGase
1 activity is unexpectedly diverted to deamidation of glutamine
residues of the substrates ( (figure 1) ). (vi)
Epoxyeicosatrienoic acid (EET) is a metabolite of P450 CYP2B19,
which has an epoxygenasae activity toward arachidonic acid in the
granular cell layer of epidermis. Exogenously added EET enhances in
situ TGase activity in cultured keratinocytes. In this case,
involucrin is preferentially used as substrate and increased CE
formation is associated [37].
Role of TGase in the cornified cell envelope formation
Cornified cell envelope formation
The CE is formed on the inner side of the plasma membrane of
keratinocytes during terminal differentiation. It is composed of a
10-nm-thick layer of a cross-linked sheath of proteins and a
5-nm-thick layer of ceramide lipids that is covalently attached to
the proteins. Various proteins, which are mostly TGase substrates,
are included in the CE.
According to the model proposed by Steinert et al., CE formation
is a precisely regulated and ordered process initiated by a rise in
intracellular Ca2+[1-3]. In the initial stage,
involucrin and desmosomal proteins such as envoplakin and
periplakin are cross-linked to produce a monomolecular layer
beneath the plasma membrane, forming a “scaffold”. Subsequently,
involucrin is cross-linked with ceramide that is replacing the
lipid bilayer at the plasma membrane. This results in fixation of
the scaffold proteins at the cell periphery. Finally, this scaffold
serves as a platform for the subsequent addition of various
reinforcement proteins, including loricrin and SPRs. These
structural proteins, before translocation to the cell periphery,
are cross-linked to form homo- and heterodimers. In the final dead
cornified cells, the completed structure is stabilized by a
covalent attachment of keratin intermediate filaments to the
CE.
Substrate proteins
Among the proteins that participated in CE formation, the major
substrate molecules are involucrin, loricrin and SPR. These
proteins have structural properties of glutamine- and lysine-rich
residues that are commonly modified by TGase.
Involucrin, the first protein to be identified as a CE
constituent, is located at or near the membrane surface to initiate
CE formation. Results of in vitro analysis have shown that
involucrin is an excellent substrate since it consists of short
peptide repeats that are rich in glutamine and lysine residues
[38]. TGase 1 is responsible for oligomerization of involucrin by
cross-linking at the initial stage of CE formation [39].
Cross-linked involucrin is deposited around the membrane surface in
the vicinity of desmosomes. Involucrin is also cross-linked to
desmosomal proteins and functions as a scaffold to which other CE
components are added later by further cross-linking to complete the
CE assembly. In later stages in CE formation, involucrin attached
to cell membrane, where TGase 1 cross-links of ceramides to
involucrin by ester bond formation [17].
Loricrin, which is an abundant protein comprising about 75% of
the total CE protein mass, is an insoluble protein and is initially
sequestered into loricrin granules. Its amino acid sequence is
unique in that the primary structure is rich in glycine, serine,
and cysteine residues [40]. In the sequence, glutamine- or
glutamine/lysine residues are also frequently observed, which is
appropriate as a TGase substrate. Indeed, loricrin is an excellent
substrate both in vivo and in vitro. The cross-linked loricrin
functions as a major reinforcement protein for the CE on the
cytoplasmic face of the structure.
Small proline-rich proteins (SPRs) consist of a multigene family
(SPR1, SPR2, SPR3 and SPR4) [41]. In the normal epidermis, SPR2
exists mainly as a CE component. SPRs possess stretches of
proline-rich repeats flanked by glutamine- and lysine rich termini,
where TGases favor these sequences for cross-linking [42]. Although
the precise roles of SPRs remain unknown, SPRs are cross-linked to
insoluble loricrin possibly contributing to movement of the
cross-linked products to the cell periphery [27].
Envoplakin and periplakin, members of the plakin family in
desmosomal proteins, are associated with plasma membrane in
suprabasal cells. Both proteins are cross-linked at the cell
periphery in differentiating keratinocytes [43]. As described
above, the reaction products provide a scaffold structure mainly
with involucrin at an early stage of CE assembly.
S100 proteins are calcium-modulated proteins that engage in
multiple regulatory activities in various cell types and tissues.
Several S100 proteins are expressed in the epidermis and may play a
role in the pathogenesis of epidermal disease [44]. Among S100
proteins, S100A11 and S100A10 are TGase substrates included in the
CE by cross-linking with various structural proteins [45]. A recent
study has shown that S100A11 is redistributed in the cell periphery
by association with microtubules upon Ca2+ stimulation
[46]. This movement along microtubules suggests a possible
mechanism by which S100A11, as a CE component, is relocated to the
cell periphery in preparation for cross-linking.
Filaggrin is also an abundant protein in keratinocytes and is
processed from a precursor by limited proteolysis during
differentiation [4, 47]. This protein functions to aggregate
keratin interfilaments into tightly aligned bundles and
macrofibriles. Analysis of CE in the human plantar epidermis shows
that filaggrin is a CE component and functions as TGase substrate
[48].
Many other TGase substrates included in CE have been
characterized: SKALP (skin-derived antileukeoproteinase)/elafin,
cystatin α, annexin I, cornifin and keratin [45, 49-52].
TGase-related-diseases
TGase 1-null mice show a defective stratum corneum and early
neonatal death [18]. It would be expected that a lack of
cross-linking activity results in a seriously pathological
phenotype since TGases play crucial roles in CE formation.
Mutations in TGase 1 are responsible for a major form of
autosomal recessive ichthyosis, termed lamellar ichthyosis (LI), a
disorder of cornification [53]. The phenotype of patients at birth
presents as a translucent colloidion membrane but later ranges from
generalized large brown plate-like scales to fine white scales with
underlying erythroderma. Since the disease is genetically
heterogeneous, various mutations in TGase 1 gene have been reported
[54-57]. These mutations produce a nonsense or truncated protein
and interfere with proteolytic activation, resulting in reduced
enzymatic activity and protein level of TGase 1.
In the case of recessive X-linked ichthyosis, CS (cholesterol
sulfate) is markedly accumulated in the epidermis due to the loss
of cholesterol sulfatase gene. As described above, excess amounts
of CS results in inhibition of cross-linking activity by TGase 1.
This observation provides evidence that the disease is caused by a
consequence of dysfunction of TGase 1 [36].
No human disease has been reported yet involving mutations in
the gene encoding TGase 3. In the case of TGase 5, irregular
expression has been reported in Darier’s disease [30].
Although abnormality is observed in the dermis, dermatitis
herpetiformis (DH) is related to TGase 3 [58]. DH is found in some
patients with celiac disease, a common chronic small intestinal
disorder. In DH patients, the granular IgA precipitates at the
papillary dermis. Sardy et al. showed that the antigen of
skin-bound IgA in DH is TGase 3 [59]. Additionally, autoantibodies
to TGase 3 are observed in the serum of patients.
Conclusion
During CE formation, the macromolecular assembly of highly
insoluble proteins is largely due to the isopeptide cross-linking
catalyzed by TGases. The isopeptide bonds are not readily cleaved
since no possible protease has been found. Therefore, these
cross-linked products provide a stable, enduring, and chemically
and mechanically resistant barrier.
Among several isozymes, TGase 1, 3 and 5 are proven participants
in CE formation. A variety of structural proteins are cross-linked
with tight substrate specificities by these different enzymes
during an orderly process of CE formation. Concomitantly, various
factors in keratinocytes, including activating proteases, regulate
the enzymatic activities of TGases ( (figure 2) ).
Although there is a considerable progress in understanding how
TGases contribute to cross-linking of the structural proteins,
various questions remain to be clarified. The proteases responsible
for the activation of TGases 1 and 3 zymogens during keratinocyte
differentiation are unknown. Some cathepsins proteolyze in vitro
but further in vivo evidence is needed. Additionally, the precise
mechanism by which the cross-linked products are coordinated to
form CE is not fully understood. Further studies on the substrate
specificity of each TGase might provide a more defined sequence of
cross-linking products during CE formation. Moreover, it is also
necessary to investigate the transport pathways of partially
cross-linked products from cytoplasm to the cell periphery for
completion of CE assembly.
Acknowledgments
The work in the author’s laboratory is supported by Grants of
Nagase Science and Technology Foundation, and TAKEDA Science
Foundation.
References
1 Steinert PM, Marecov LN. Initiation of assembly of the
cell envelope barrier structure of stratified squamous epithelia.
Mol Biol Cell 1999; 10: 4247-61.
2 Kalinin AE, Andrey VK, Steinert PM. Epithelial
barrier function: assembly and structural features of the cornified
envelope. Bioessays 2002; 24: 789-800.
3 Candi E, Schmidt R, Melino G. The cornified
envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol
2005; 6: 328-40.
4 Preseland RB, Dale BA. Epithelial structural
proteins of the skin and oral cavity: function in health and
disease. Crit Rev Oral Biol Med 2000; 11: 383-408.
5 Zeeuwen PL. Epidermal differentiation: the role of
proteases and their inhibitors. Eur J Cell Biol 2004; 83:
761-73.
6 Lorand L, Graham RM. Transglutminases: crosslinking
enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 2003; 4:
140-56.
7 Griffin M, Casadio R, Bergamini CM.
Transglutaminases: Nature’s biological glues. Biochem J 2002; 368:
377-96.
8 Eckert RL, Sturniolo MT, Broome AM,
Ruse M, Rorke EA. Transglutaminase function in epidermis.
J Invest Dermatol 2005; 124: 481-92.
9 Stephens P, Grenard P, Aeschlimann P,
Langley M, Blain E, Errington R, et al.
Crosslinking and G-protein functions of transglutaminase 2
contribute differentially to fibroblast wound healing responses. J
Cell Sci 2004; 117: 3389-403.
10 Kim SY, Chung SI, Steinert PM. Highly active
soluble processed forms of the transglutaminase 1 enzyme in
epidermal keratinocytes. J Biol Chem 1995; 270: 18026-35.
11 Kim SY, Bae C-D. Calpain inhibitors reduce the
cornified envelope formation by inhibiting proteolytic processing
of transglutaminase 1. Exp Mol Med 1998; 30: 257-62.
12 Egberts F, Heinrich M, Jensen JM,
Winoto-Morbach S, Pfeiffer S, Wickel M, et al.
Cathepsin D is involved in the regulation of transglutaminase 1 and
epidermal differentiation. J Cell Sci 2004; 117: 2295-307.
13 Thacher SM, Rice RH. Keratinocyte-specific
transglutaminase of cultured human epidermal cells: relation to
cross-linked envelope formation and terminal differentiation. Cell
1985; 40: 685-95.
14 Steinert PM, Chung SI, Kim SY. Inactive
zymogen and highly active proteolytically processed membrane-bound
forms of the transglutaminase 1 enzyme in human epidermal
keratinocytes. Biochem Biophys Res Commun 1996; 221: 101-6.
15 Iizuka R, Chiba K, Ohmi-Imajoh S. A novel
approach for the detection of proteolytically activated
transglutaminase 1 in epidermis using cleavage site-directed
antibodies. J Invest Dermatol 2003; 121: 457-64.
16 Steinert PM, Kim SY, Chung SI,
Marekov LN. The transglutaminase 1 enzyme is variably acylated
by myristate and palmitate during differentiation in epidermal
keratinocytes. J Biol Chem 1996; 271: 26242-50.
17 Nemes Z, Marekov LN, Fesus L,
Steinert PM. A novel function for transglutaminase 1:
attachment of long-chain omega-hydroxyceramides to involucrin by
ester bond formation. Proc Natl Acad Sci USA 1999; 96: 8402-7.
18 Matsuki M, Yamashita F, Ishida-Yamamoto A,
Yamada K, Kinoshita C, Fushiki S, et al.
Defective stratum corneum and early neonatal death in mice lacking
the gene for transglutaminase 1. Proc Natl Acad Sci USA 1998; 95:
1044-9.
19 Kim HC, Lewis MS, Gorman JJ, Park SC,
Girard JE, Folk JE, et al. Protransglutaminase E
from guinea pig skin. Isolation and partial characterization. J
Biol Chem 1990; 265: 21971-8.
20 Kim IG, Gorman JJ, Park SC, Chung SI,
Steinert PM. The deduced sequence of the novel
protransglutaminase E (TGase3) of human and mouse. J Biol Chem
1993; 268: 12682-90.
21 Ahvazi B, Kim HC, Kee SH, Nemes Z,
Steinert PM. Three-dimensional structure of the human
transglutaminase 3 enzyme: binding of calcium ions changes
structure for activation. EMBO J 2002; 21: 2055-67.
22 Hitomi K, Kanehiro S, Ikura K, Maki M.
Characterization of recombinant mouse epidermal-type
transglutaminase (TGase 3): regulation of its activity by
proteolysis and guanine nucleotides. J Biochem (Tokyo) 1999; 125:
1048-54.
23 Zeeuwen PL, van Vlijmen-Willems IM, Olthuis D,
Johansen HT, Hitomi K, Hara-Nishimura I,
Powers JC, James KE, Op den Camp HJ, Lemmens R,
Schalkwijk J. Evidence that unrestricted legumain activity is
involved in disturbed epidermal cornification in cystatin M/E
deficient mice. Hum Mol Genet 2004; 13: 1069-79.
24 Hitomi K, Horio Y, Ikura K, Maki M.
Analysis of epidermal-type transglutaminase expression in mouse
tissues and cell lines. Int J Biochem Cell Biol 2001; 33:
491-8.
25 Hitomi K, Presland RB, Nakayama T,
Fleckman P, Dale BA, Maki M. Analysis of
epidermal-type transglutaminase (transglutaminase 3) in human
stratified epithelia and cultured keratinocytes using monoclonal
antibodies. J Dermatol Sci 2003; 32: 95-103.
26 Candi E, Melino G, Mei G, Tarcsa E,
Chung SI, Marekov LN, et al. Biochemical,
structural, and transglutaminase substrate properties of human
loricrin, the major epidermal cornified cell envelope protein. J
Biol Chem 1995; 270: 26382-90.
27 Candi E, Tarcsa E, Idler WW, Kartasova T,
Marekov LN, Steinert PM. Transglutaminase cross-linking
properties of the small proline-rich 1 family of cornified cell
envelope proteins. Integration with loricrin. J Biol Chem 1999;
274: 7226-37.
28 Aeschlimann D, Koeller MK, Allen-Hoffmann BL,
Mosher DF. Isolation of a cDNA encoding a novel member of the
transglutaminase gene family from human keratinocytes. Detection
and identification of transglutaminase gene products based on
reverse transcription-polymerase chain reaction with degenerate
primers. J Biol Chem 1998; 273: 3452-60.
29 Candi E, Oddi S, Terrinoni A, Paradisi A,
Ranalli M, Finazzi-Agro A, et al. Transglutaminase 5
cross-links loricrin, involucrin, and small proline-rich proteins
in vitro. J Biol Chem 2001; 276: 35014-23.
30 Candi E, Oddi S, Paradisi A, Terrinoni A,
Ranalli M, Teofoli P, et al. Expression of
transglutaminase 5 in normal and pathologic human epidermis. J
Invest Dermatol 2002; 119: 670-7.
31 Candi E, Paradisi A, Terrinoni A,
Pietroni V, Oddi S, Cadot B, et al.
Transglutaminase 5 is regulated by guanine-adenine nucleotides.
Biochem J 2004; 381: 313-9.
32 Rossi A, Catani MV, Candi E,
Bernassola F, Puddu P, Melino G. Nitric oxide
inhibits cornified envelope formation in human keratinocytes by
inactivating transglutaminases and activating protein 1. J Invest
Dermatol 2000; 115: 731-9.
33 Higuchi K, Kawashima M, Takagi Y,
Kondo H, Yada Y, Ichikawa Y, et al.
Sphingosylphosphorylcholine is an activator of transglutaminase
activity in human keratinocytes. J Lipid Res 2001; 42: 1562-70.
34 Sturniolo MT, Dashti SR, Deucher A,
Rorke EA, Broome AM, Chandraratna RA, et al. A
novel tumor suppressor protein promotes keratinocyte terminal
differentiation via activation of type I transglutaminase. J Biol
Chem 2003; 278: 48066-73.
35 Kawabe S, Ikuta T, Ohba M, Chida K,
Ueda E, Yamanishi K, et al. Cholesterol sulfate
activates transcription of transglutaminase 1 gene in normal human
keratinocytes. J Invest Dermatol 1998; 111: 1098-102.
36 Nemes Z, Demeny M, Marekov LN, Fesus L,
Steinert PM. Cholesterol 3-sulfate interferes with cornified
envelope assembly by diverting transglutaminase 1 activity from the
formation of cross-links and esters to the hydrolysis of glutamine.
J Biol Chem 2000; 275: 2636-46.
37 Ladd PA, Du L, Capdevila JH, Mernaugh R,
Keeney DS. Epoxyeicosatrienoic acids activate
transglutaminases in situ and induce cornification of epidermal
keratinocytes. J Biol Chem 2003; 278: 35184-92.
38 Eckert RL, Green H. Structure and evolution of the
human involucrin gene. Cell 1986; 46: 583-9.
39 Steinert PM, Marekov LN. Direct evidence that
involucrin is a major early isopeptide cross-linked component of
the keratinocyte cornified cell envelope. J Biol Chem 1997; 272:
2021-30.
40 Hohl D, Mehrel T, Lichti U, Turner ML,
Roop DR, Steinert PM. Characterization of human loricrin.
Structure and function of a new class of epidermal cell envelope
proteins. J Biol Chem 1991; 266: 6626-36.
41 Cabral A, Voskamp P, Cleton-Jansen AM,
South A, Nizetic D, Backendorf C. Structural
organization and regulation of the small proline-rich family of
cornified envelope precursors suggest a role in adaptive barrier
function. J Biol Chem 2001; 276: 19231-7.
42 Tarcsa E, Candi E, Kartasova T, Idler WW,
Marekov LN, Steinert PM. Structural and transglutaminase
substrate properties of the small proline-rich 2 family of
cornified cell envelope proteins. J Biol Chem 1998; 273:
23297-303.
43 Kalinin AE, Idler WW, Marekov LN,
McPhie P, Bowers B, Steinert PM, et al.
Co-assembly of envoplakin and periplakin into oligomers and Ca
(2+)-dependent vesicle binding: implications for cornified cell
envelope formation in stratified squamous epithelia. J Biol Chem
2004; 279: 22773-80.
44 Eckert RL, Broome AM, Ruse M, Robinson N,
Ryan D, Lee K. S100 proteins in the epidermis. J Invest
Dermatol 2004; 123: 23-33.
45 Robinson NA, Lapic S, Welter JF,
Eckert RL. S100A11, S100A10, annexin I, desmosomal proteins,
small proline-rich proteins, plasminogen activator inhibitor-2, and
involucrin are components of the cornified envelope of cultured
human epidermal keratinocytes. J Biol Chem 1997; 272: 12035-46.
46 Broome AM, Eckert RL. Microtubule-dependent
redistribution of a cytoplasmic cornified envelope precursor. J
Invest Dermatol 2004; 122: 29-38.
47 Presland RB, Haydock PV, Fleckman P,
Nirunsuksiri W, Dale BA. Characterization of the human
epidermal profilaggrin gene. Genomic organization and
identification of an S-100-like calcium binding domain at the amino
terminus. J Biol Chem 1992; 267: 23772-81.
48 Simon M, Haftek M, Sebbag M, Montezin M,
Girbal-Neuhauser ESchmitt D, et al. Evidence that
filaggrin is a component of cornified cell envelopes in human
plantar epidermis. Biochem J 1996; 317: 173-7.
49 Zeeuwen PL, Hendriks W, de Jong WW,
Schalkwijk J. Identification and sequence analysis of two new
members of the SKALP/elafin and SPAI-2 gene family. Biochemical
properties of the transglutaminase substrate motif and suggestions
for a new nomenclature. J Biol Chem 1997; 272: 20471-8.
50 Takahashi M, Tezuka T, Katunuma N. Filaggrin
linker segment peptide and cystatin alpha are parts of a complex of
the cornified envelope of epidermis. Arch Biochem Biophys 1996;
329: 123-6.
51 Austin SJ, Fujimoto W, Marvin KW, Vollberg TM, Lorand L,
Jetten AM. Cloning and regulation of cornifin beta, a new member of
the cornifin/spr family. Suppression by retinoic acid
receptor-selective retinoids J Biol Chem 199; 271: 3737-42.
52 Candi E, Tarcsa E, Digiovanna JJ,
Compton JG, Elias PM, Marekov LN, et al. A
highly conserved lysine residue on the head domain of type II
keratins is essential for the attachment of keratin intermediate
filaments to the cornified cell envelope through isopeptide
crosslinking by transglutaminases. Proc Natl Acad Sci USA 1998; 95:
2067-72.
53 Huber M, Rettler I, Bernasconi K,
Frenk E, Lavrijsen SP, Ponec M, et al.
Mutations of keratinocyte transglutaminase in lamellar ichthyosis.
Science 1995; 267: 525-8.
54 Russell LJ, DiGiovanna JJ, Rogers GR,
Steinert PM, Hashem N, Compton JG, et al.
Mutations in the gene for transglutaminase 1 in autosomal recessive
lamellar ichthyosis. Nat Genet 1995; 9: 279-83.
55 Huber M, Yee VC, Burri N, Vikerfors E,
Lavrijsen AP, Paller AS, et al. Consequences of
seven novel mutations on the expression and structure of
keratinocyte transglutaminase. J Biol Chem 1997; 272: 21018-26.
56 Candi E, Melino G, Lahm A, Ceci R,
Rossi A, Kim IG, et al. Transglutaminase 1 mutations
in lamellar ichthyosis. Loss of activity due to failure of
activation by proteolytic processing. J Biol Chem 1998; 273:
13693-702.
57 Akiyama M, Takizawa Y, Suzuki Y,
Ishiko A, Matsuo I, Shimizu H. Compound heterozygous
TGM1 mutations including a novel missense mutation L204Q in a mild
form of lamellar ichthyosis. J Invest Dermatol 2001; 116:
992-5.
58 Karpati S. Dermatitis herpetiformis: close to
unravelling a disease. J Dermatol Sci 2004; 34: 83-90.
59 Sardy M, Karpati S, Merkl B, Paulsson M,
Smyth N. Epidermal transglutaminase (TGase 3) is the
autoantigen of dermatitis herpetiformis. J Exp Med 2002; 195:
747-57.
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