Elevated cyclins and cyclin-dependent kinase activity in the XXXX cell line RD.

@entity9171 @entity4998 @entity986 @entity5 @entity8985 @entity15308 @entity13525 @entity980 @entity994 @entity995
An important early event in the differentiation of skeletal muscle cells is exit from the cell cycle, after which full expression of the muscle phenotype occurs. @entity980 ( @entity980 ), a @entity5 of skeletal muscle origin, expresses a number of muscle-specific proteins, including @entity9171 ; however, these cells fail to arrest or differentiate when cultured in @entity4998 ( @entity4998 ). To determine the basis for the failure of @entity980 cells to differentiate or arrest, we studied the molecular response of the embryonal @entity980 cell line, RD, to culture in @entity4998 . Under these conditions, the @entity995 ( @entity995 ) was primarily in the hyperphosphorylated state. This is in contrast to myoblasts cultured in @entity4998 , in which the hypophosphorylated form of @entity995 is exclusively present. Measurements of the expression and activities of cyclin-dependent kinases (cdks) @entity15308 and @entity8985 indicated that RD cells maintained higher levels than do myoblasts, and the activity and abundance of these proteins did not significantly decrease upon culture in @entity4998 in RD cells, as they did in myoblasts. Similarly, elevated expression of cyclins D1, E, and A was observed in RD cells. Interestingly, cdk inhibitors are expressed in RD cells, with @entity986 expression markedly elevated relative to myoblasts. Ectopic expression of @entity994 , @entity986 , or @entity13525 caused a growth arrest of RD cells but not detectable expression of a myogenic marker. Furthermore, a constitutively active @entity995 protein could also inhibit the growth of RD cells without inducing myogenic differentiation. Taken together, these data suggest that the elevated levels of @entity15308 and/or @entity8985 observed in RD cells contribute to the inability of RD cells to growth arrest when cultured in @entity4998 but that these activities alone are not responsible for the failure of RD cells to differentiate.
