Cyclin A, cell cycle control and oncogenesis.
One of the most fundamental questions in biology is how a cell is able to regulate its division cycle. Initially it was thought that in mammalian cells control over entry into the cell cycle is exerted at a restriction point in G1; once past this point the cell would be free to undergo all the steps needed until the following division. Hence, for many years research on tumorigenesis focused on the mitogenic activation of quiescent cells by growth factors, peptide hormones and oncogene products (for reviews see [1, 2]). These studies investigated the initial steps required to induce a quiescent, nondividing cell to proliferate, and led to the identification of many growth factor receptors, of both the tyrosine kinase family and the G-protein coupled family. Receptors bearing protein tyrosine phosphatase or serine kinase catalytic domains were also identified via this route (for reviews see [3, 4, 5]). However more recent studies on the cooperation between different growth factors for mitogenesis have shown that multiple requirements exist for a cell to proceed through the entire division cycle. Indeed studies in several different organisms, pioneered by investigators working with Ascomycetes [6, 7, 8], have now clearly shown that the eukaryotic cell cycle proceeds through multiple check-points. Furthermore, it now appears that many of the regulatory elements and even pathways have been conserved throughout evolution. In this review we discuss the possible involvement of one of the transducing molecules, cyclin A, in abnormal cell proliferation.
Pagano
M
M
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Draetta
G
G
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D016213:Cyclins / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D016213:Cyclins; D016203:CDC2 Protein Kinase