TIG3: an important regulator of keratinocyte proliferation and survival.

Tazarotene-induced gene 3 (TIG3) is a tumor suppressor protein. In normal human epidermis, TIG3 is present in the differentiated, suprabasal layers, and it regulates terminal differentiation. TIG3 level is reduced in hyperproliferative diseases, including psoriasis and skin cancer, suggesting that loss of TIG3 is associated with enhanced cell proliferation. Moreover, transient expression of TIG3 leads to terminal differentiation in normal keratinocytes and apoptosis in skin cancer cells. In both cell types, TIG3 distributes to the cell membrane and to the centrosome. At the cell membrane, TIG3 interacts with and activates type I transglutaminase to enhance keratinocyte terminal differentiation. TIG3 at the centrosome acts to inhibit centrosome separation during mitosis and to alter microtubule function. These findings argue that TIG3 is involved in the control of keratinocyte differentiation and that loss of TIG3 in transformed cells contributes to the malignant phenotype.