A new perspective on cyclin D1: Beyond cell cycle regulation

The canonical function of cyclin D1 in regulating cell cycle progression was well established in the 1990s. The role of cyclin D1 has been expanded in the last decade. The novel functions of cyclin D1 include regulation of hormone signaling through cross talk with nuclear receptors and cofactors, gene transcription through direct interaction with transcription factors, cell migration and invasion, cell death, angiogenesis, mitochondrial metabolism, DNA damage and repair, and chromosomal instability (CIN). High-throughput analysis, including whole-genome expression profiling and deep sequencing, identified cyclin D1 binding sites in the context of local chromatin. Proteomics and protein arrays identified cyclin D1-interacting proteins, which confirmed both known interactive proteins involved in cell cycle regulation and a number of new proteins. These novel experimental approaches revealed previously unrecognized functions of cyclin D1 which may contribute to the role of cyclin D1 in tumorigenesis. Herein, we discuss recent findings on the role of cyclin D1 in regulating metabolism, DNA damage, and CIN and how these processes may guide novel clinical management.