Keratins play a critical structural role preserving the integrity of the epidermis. Mutations in these intermediate filament proteins are associated with skinblistering syndromes such as epidermolysis bullosa simplex (EBS), and mice lacking keratin 5 or keratin 14 exhibit characteristic skin fragility. Keratin 10 (K10) knockouts, by contrast, have relatively normal skin, because compensatory mechanisms increase the levels of other keratins. Julia Reichelt and Thomas Magin now reveal that K10-/- mice do, however, have a much more surprising defect: hyperproliferation of the epidermis, which is accompanied by elevated expression of the transcription factor MYC and its target cyclin D1 in keratinocytes (see). Significantly, it is the basal keratinocytes that hyperproliferate — rather than the neighbouring suprabasal cells in which K10 is normally present. K10 thus has a novel role in cell cycle control but acts indirectly. Reichelt and Magin propose that the loss of K10 causes suprabasal keratinocytes to transmit a chemical or mechanical signal that stimulates MYC expression and consequent hyperproliferation of the basal keratinocytes below.
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