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Michael T Sturniolo

Publications and source records attributed to Michael T Sturniolo.

5 recordsLinked to original sources
PubMed2005

A novel transglutaminase activator forms a complex with type 1 transglutaminase.

Type I transglutaminase is a plasma membrane-anchored intracellular protein-protein crosslinking enzyme that is responsible for assembly of the keratinocyte cornified envelope during terminal keratinocyte differentiation. We recently described a novel protein, TIG3, that when expressed in keratinocytes causes increased transglutaminase activity and keratinocyte cell death. However, the mechanism of activation of transglutaminase by TIG3 is not known. We now extend our previous study and show that full-length TIG3 forms a complex with type I transglutaminase that is demonstrated by TIG3-transglutaminase co-precipitation. We also demonstrate that treating TIG3-expressing cells with monodansyl cadaverine, a competitive transglutaminase substrate, attenuates the TIG3-dependent response, suggesting that transglutaminase is an important mediator of TIG3 action. These findings suggest that TIG3 forms a complex with transglutaminase resulting in transglutaminase activation and that transglutaminase activity is required for the TIG3-dependent biological response.

Enzyme Activators↗
PubMed2005

Human epidermal keratinocytes undergo (-)-epigallocatechin-3-gallate-dependent differentiation but not apoptosis.

Epigallocatechin-3-gallate (EGCG) is an important chemopreventive agent derived from green tea. We recently reported that EGCG treatment enhances keratinocyte differentiation as evidenced by increased human involucrin promoter activity [Balasubramanian,S., Efimova,T. and Eckert,R.L. (2002) J. Biol. Chem., 277, 1828-1836]. In the present paper, we extend these findings and show that EGCG also increases the expression of other differentiation markers-procaspase 14 and type I transglutaminase (TG1). Both TG1 mRNA and protein level, and activity are increased by treatment with EGCG. Increased TG1 activity is evidenced by a direct transglutaminase assay, and by the ability of EGCG to stimulate the covalent incorporation of fluorescein cadaverine substrate into crosslinked intracellular structures. In contrast, type II transglutaminase levels are not altered by EGCG treatment. We also assessed whether EGCG promotes keratinocyte apoptosis. We show that EGCG treatment does not promote the cleavage of procaspase-3, -8, -9 or poly(ADP-ribose) polymerase. Moreover, treatment with the pan-caspase inhibitor, Z-VAD-FMK, does not reverse the EGCG-associated reduction in cell viability. In addition, there is no increase in cells having sub-G(1)/S DNA content, and no evidence for the release of cytochrome c from the mitochondria. These findings confirm, using several endpoints, that EGCG treatment enhances normal keratinocyte differentiation but does not promote apoptosis.

Apoptosis↗
PubMed2005

Transglutaminase function in epidermis.

Surface epithelial cells, such as the epidermal keratinocyte, undergo a process of terminal cell differentiation that results in the construction of a multilayered epithelium. This epithelium functions to protect the organism from the environment. Transglutaminases, enzymes that catalyze the formation of isopeptide protein-protein cross-links, are key enzymes involved in the construction of this structure. This brief review will focus on the role of these enzymes in constructing the epidermal surface.

Epidermal Cells↗
PubMed2003

A novel tumor suppressor protein promotes keratinocyte terminal differentiation via activation of type I transglutaminase.

Tazarotene-induced protein 3 (TIG3) is a recently discovered regulatory protein that is expressed in the suprabasal epidermis. In the present study, we show that TIG3 regulates keratinocyte viability and proliferation. TIG3-dependent reduction in keratinocyte viability is accompanied by a substantial increase in the number of sub-G1 cells, nuclear shrinkage, and increased formation of cornified envelope-like structures. TIG3 localizes to the membrane fraction, and TIG3-dependent differentiation is associated with increased type I transglutaminase activity. Microscopic localization and isopeptide cross-linking studies suggest that TIG3 and type I transglutaminase co-localize in membranes. Markers of apoptosis, including caspases and poly(ADP-ribose) polymerase, are not activated by TIG3, and caspase inhibitors do not stop the TIG3-dependent reduction in cell viability. Truncation of the carboxyl-terminal membrane-anchoring domain results in a complete loss of TIG3 activity. The morphology of the TIG3-positive cells and the effects on cornified envelope formation suggest that TIG3 is an activator of terminal keratinocyte differentiation. Our studies suggest that TIG3 facilitates the terminal stages in keratinocyte differentiation via activation of type I transglutaminase.

Adenoviridae↗