The role of p27kip1 in the in vitro differentiation of murine keratinocytes

We have studied the regulation of cyclins and cyclindependent kinase activities during differentiation of primary mouse keratinocytes. Differentiation was induced by placing primary munne keratinocytes into suspension culture, under conditions which prevent cells from attaching to any surface. This treatment induces synthesis of keratin I , one of the earliest known markers of keratinocyte differentiation, and also results in a profound change in the regulation of G1 and S-phase cyclins and their associated proteins as well as their activfties. The placement of cells in suspension culture reduced cyclin A, Dl , and E kinase activity within 6 h, accompanied by the cessation of DNA synthesis. KI mRNA levels were observed to increase after this period, supporting the hypothesis