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Tazarotene-Induced Gene 3: A Novel Regulator of Keratinocyte Differentiation

Sturniolo, Michael Thomas
http://rave.ohiolink.edu/etdc/view?acc_num=case1100296278

Abstract Details

2005, Doctor of Philosophy, Case Western Reserve University, Molecular Virology.
Tazarotene-induced gene 3 (TIG3) is a novel regulatory protein expressed in the human epidermis. TIG3 expression in keratinocytes results in a decrease in both proliferation and cell viability. The mortality following TIG3 expression occurs in the absence of the activation of apoptosis associated caspases. Keratinocytes expressing TIG3 display striking morphologic changes. The changes in morphology are consistent with insoluble cell ghost formation, or a differentiation-like state, and are associated with an increase in transglutaminase type 1 (TG1) activation. Microscopic localization and isopeptide crosslinking studies reveal a colocalization between TIG3 and TG1 in the particulate phase of keratinocytes. Immunoprecipitation reveals that TIG3 and TG1 are present within a similar protein complex. Inhibition of TIG3-induced TG activity with the small molecule competitive substrate, monodansylcadaverine (MDC), demonstrates that the loss in cell viability, morphologic changes, and crosslinking are transglutaminase dependent. A truncated form of TIG3, which lacks the C-terminal hydrophobic domain, is biologically inactive. This truncated TIG3 does not properly localize, indicating a role for the hyprophobic domain, in particulate phase association. In addition, TIG3 can serve as a substrate for active transglutaminases, as demonstrated by the covalent attachment of the transglutaminase substrate biotin-x-cadaverine to TIG3. The TIG3-induced TG1 activity occurs in the absence of elevated extracellular calcium levels, indicating an altered calcium requirement in TG1 activation. The studies presented here suggest that TIG3 may act to facilitate keratinocyte differentiation through the activation of transglutaminase type 1.
Richard Eckert (Advisor)
Biology, Cell
TIG3; Transglutaminase; Keratinocyte

Recommended Citations

Citations

  • Sturniolo, M. T. (2005). Tazarotene-Induced Gene 3: A Novel Regulator of Keratinocyte Differentiation [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1100296278

    APA Style (7th edition)

  • Sturniolo, Michael. Tazarotene-Induced Gene 3: A Novel Regulator of Keratinocyte Differentiation. 2005. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1100296278.

    MLA Style (8th edition)

  • Sturniolo, Michael. "Tazarotene-Induced Gene 3: A Novel Regulator of Keratinocyte Differentiation." Doctoral dissertation, Case Western Reserve University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1100296278

    Chicago Manual of Style (17th edition)

case1100296278
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© 2004, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.