Assembly in the Cyclic Adenosine Monophosphate–dependent Proliferation of Thyrocytes

In different systems, cyclic adenosine mono-phosphate (cAMP) either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epi-thelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S prereplicative phase progression by cAMP as a second messenger for thyrotropin (TSH). The cAMP-depen-dent mitogenic pathway is unique as it is independent of mitogen-activated protein kinase activation and differs from growth factor–dependent pathways at the level of the expression of several protooncogenes/tran-scription factors. This study examined the involvement of D-type G1 cyclins and their associated cyclin-depen-dent kinase (cdk4) in the cAMP-dependent G1 phase progression of dog thyroid cells. Unlike epidermal growth factor (EGF) 1 serum and other cAMP-inde-pendent mitogens, TSH did not induce the accumula-tion of cyclins D1 and D2 and partially inhibited the basal expression of the most abundant cyclin D3. How-ever, TSH stimulation enhanced the nuclear detection of cyclin D3. This effect correlated with G1 and S phase progression. It was found to reflect both the unmasking of an epitope of cyclin D3 close to its domain of interac-tion with cdk4, and the nuclear translocation of cycli