摘要：

Cyclins are key components of the cell cycle progression machinery. They activate their partner cyclin-dependent kinases (CDKs) and possibly target them to respective substrate proteins within the cell. CDK-mediated phosphorylation of specific sets of proteins drives the cell through particular phases or checkpoints of the cell cycle. During unperturbed growth of normal cells, the timing of expression of several cyclins is discontinuous, occurring at discrete and well-defined periods of the cell cycle. lmmunocytochemical detection of cyclins in relation to cell cycle position (DNA content) by multiparameter how cytometry has provided a new approach to cell cycle studies. This approach, like no other method, can be used to detect the unscheduled expression of cyclins, namely, the presentation of G(1) cyclins by cells in G(2)/M and of G(2)/M cyclins by G(1) cells, without the need for cell synchronization. Such unscheduled expression of cyclins B1 and A was seen when cell cycle progression was halted, e.g., after synchronization at the G(1)/S boundary by inhibitors of DNA replication. The unscheduled expression of cyclins hi or E, but not of A, was also observed in some tumor cell lines even when their growth was unperturbed. Likewise, whereas the expression of cyclins D1 or D3 in nontumor cells was restricted to an early section of G(1), the presentation of these proteins in many tumor cell lines also was seen during S and G(2)/M. This suggests that the partner kinase CDK4 (which upon activation by D-type cyclins phosphorylates pRB committing the cell to enter S) is perpetually active throughout the cell cycle in these tumor lines. Expression of cyclin D also may serve to discriminate G(0) vs. G(1) cells and, as an activation marker, to identify the mitogenically stimulated cells entering the cell cycle. Differences in cyclin expression make it possible to discriminate between cells having the same DNA content but residing at different phases such as in G(2) vs. M or

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