Upregulation of Class II β-Tubulin Expression in Differentiating Keratinocytes

Abstract

The diverse functions of microtubules (MT) in different cells and tissues may be facilitated by compositional changes in tubulin isotypes. We obtained partial cDNA clones of class II beta-tubulin from a library of differentiating normal human epidermal keratinocytes (NHEK) cells, whereas screening via subtractive hybridization for genes involved in calcium-induced keratinocyte differentiation. Analysis of the isotypic composition of beta-tubulin from NHEK cells revealed elevations in class II beta-tubulin concentrations at both protein and message levels during cell differentiation, resulting in increased rates of incorporation of class II beta-tubulin into MT. Immunohistochemistry of normal and pathologic skin tissues showed that class II beta-tubulin occurred in the granular layer of the epidermis and in differentiated areas of carcinomas. Class II beta-tubulin was, however, not observed in the uppermost granular and cornified layers of normal epidermis. Further experiments showed that MT were likely to decay in the final stage of terminal differentiation during formation of the cornified envelope. Our results suggest that there is differential modulation of MT composition and stability during keratinocyte differentiation.

Expression of class II β‐tubulin in non‐melanoma cutaneous tumors

“…We previously demonstrated that class II tubulin expression is up-regulated during keratinocyte squamous differentiation using subtractive hybridization. 5,6,14 In accord with that report, IHC in this study showed that class II tubulin expression was concentrated in the granular layer of the epidermis and the inner areas of the follicular infundibulum.…”

“…Among these, class II β‐tubulin (class II tubulin), a major neuronal tubulin, 4 is expressed more abundantly in differentiated keratinocytes than in non‐differentiated keratinocytes 5 . This suggests that the expression of class II tubulin may be useful for monitoring the differentiation status of keratinocytes in normal skin and in squamous differentiated tumors 5 . However, the expression of class II tubulin has not been fully elucidated in other epidermal or dermal components, such as melanocytes or hair follicles.…”

“…5 This suggests that the expression of class II tubulin may be useful for monitoring the differentiation status of keratinocytes in normal skin and in squamous differentiated tumors. 5 However, the expression of class II tubulin has not been fully elucidated in other epidermal or dermal components, such as melanocytes or hair follicles.…”

Aberrant expression of class III β-tubulin in basal cell carcinoma of the skin

“…Roh et al reported that ß II was focally expressed in approximately half of BCCs (32/57 cases) (19). However, ß II expression is not directly associated with neuroendocrine differentiation in the cutaneous tumors, because ß II is expressed in the keratinocytes of the granular layer, hair cortical and cuticular cells, inner root sheath and companion layer of the outer root sheath in the normal skin and up-regulated during squamous differentiation of keratinocytes (20). Roh et al also reported that ß II expression was increased in the areas of squamous or follicular differentiation in the cutaneous tumors (19).…”

Post-translational control of Myc function during differentiation

“…59 In these tissues, Myc-nick may be involved in mediating at least some of the functions attributed to the myc gene in terminal differentiation and tissue maintenance. Furthermore, during keratinocyte differentiation calpains are activated 28 and there is an increase in tubulin acetylation, 62 suggesting a correlation with Myc-nick production and function. In a keratinocyte model for the autoimmune disease Pemphigus vulgaris, a smaller form of Myc, with a size corresponding to that of Myc-nick, was detected predominantly in the cytoplasm.…”