Multiple molecular levels of cell cycle regulation.

The objective of this brief review is to stress the importance of multiple levels of molecular regulation of complex processes such as cell growth and to illustrate their derangements as they occur in cancer cells. One major research emphasis today is the regulation of transcription by binding of transactivating proteins to promoter motifs. Another focus is on the multiple roles of protein phosphorylations in signal transduction pathways. Evidence is strong, however, that major controls exist at numerous other molecular levels as well (Fig. 1). These include pre-mRNA processing, pre-mRNA degradation, mRNA degradation, control of translation, permanent protein modifications, protein degradation, reversible covalent protein alterations, noncovalent interactions with small molecules and with other proteins, and effects of relocations into cell compartments. These controls are exhibited in all biological processes. A few illustrative examples are briefly discussed, which come mainly from our researches in the area of cell cycle regulation and its derangement in cancer.