Cyclins: Roles in mitogenic signaling and oncogenic transformation

Cyclins are the regulatory subunits of kinases that control progress through the cell cycle. This review focuses on cyclins that are targets for extracellular signaling and frequently deregulated during oncogenesis, particularly cyclin D1. Receptor tyrosine kinases and adhesion molecules act through various effector pathways to modulate cyclin D1 abundance at multiple levels including transcription, translation and protein stability. In contrast, cyclin E-Cdk2 activity appears to be more commonly regulated by means other than regulation of cyclin E abundance. The importance of these pathways during oncogenesis is illustrated by the dependence of oncogenes such as Ras and Neu/ErbB2 on cyclin D1. Thus, understanding the roles of cyclins in growth factor and adhesion signaling is important for understanding the biology of both normal and neoplastic cells.