Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases

Abstract

In addition to their well-established functions in driving cell proliferation, cell cycle proteins have several non-canonical roles. D-type cyclins and their partner cyclin-dependent kinase 6 (CDK6) have direct, kinase-independent roles in augmenting or repressing gene expression. In mammalian cells, cyclin D1 promotes, whereas cyclin A–CDK2 inhibits, DNA double-strand break (DSB) repair through homologous recombination. In yeast, CDK activity seems to dictate the choice of DSB repair between non-homologous end-joining and homologous recombination. Cyclins are postulated to regulate apoptosis, autophagy and anoikis. Analyses of mice lacking D-type cyclins support pro-survival roles for these proteins in specific tissues. Cyclin D1, CDK6 and the CDK inhibitor p27 (KIP1) can affect the actin cytoskeleton and cell migration through several mechanisms. Cell cycle proteins have important roles in development and have important functions in the nervous system and in regulating the immune response. Cyclins and CDKs are shown or postulated to regulate metabolism through different routes, including a direct role in controlling mitochondrial function.