ReviewCell-cycle inhibitors: three families united by a common cause
Section snippets
Cell cycle: making decisions
In a tissue, a cell simultaneously receives multiple signals, some mitogenic and some anti-mitogenic. These inputs exist as both soluble extracellular factors, such as growth factors or hormones, and as physical forces of interaction with other cells or with the substratum. At a certain point in G1, the restriction point (Pardee, 1989), these signals culminate in a molecular mechanism that allows only a binary decision—to either commit to the mitotic cell cycle and enter S-phase, or to not
What mice tell us
Most of the biochemical work characterizing cell-cycle machinery components comes from studies in cell culture using immmortalized or transformed cell lines. However, the ‘noise’ of the genetic alterations that led to inmortalization or transformation can affect the observations and cannot be ignored. Thus, studies carried out in a more ‘normal’ biologic context are essential. Targeted mutagenesis in mouse provides a powerful tool for discovering the roles of cell-cycle regulators in
Conclusions
Information about the role of the CDK inhibitors and the pRb family of proteins in a physiological context is limited. The simplest situations of redundancy may not be distinguished without extensive and costly genetics, and the assessment of the relationships between the proteins vis-à-vis a process, be it proliferation or something else, such as apoptosis or differentiation must be determined in a cell-type-specific manner. In contrast, the biochemical features of these proteins and their
Acknowledgements
We apologize to those whose work has been cited indirectly by space limitations. We also thank Martine F. Roussel and Gino Vairo for sharing results before publication and members of our laboratory by continuous discussion. A.V. is a recipient of a postdoctoral fellowship from the Ministerio de Educacion y Cultura from Spain.
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