Functional interaction of the retinoblastoma protein with mammalian D-type cyclins

Article Abstract:

Cyclins D2 and D3 can efficiently form specific complexes with the retinoblastoma (Rb) gene product in vitro. This complex formation partially depends on the integrity of a major protein-binding domain of Rb necessary for its growth-suppressive activity. The coexpression of cyclin D2 and Rb in Rb-negative human osteosarcoma cells triggers Rb phosphorylation and a reversal of its ability to suppress G1 exit. These findings indicate that at least one D-type cyclin species regulate cell growth and that unphosphorylated Rb is an active, growth inhibitory species.

Phosphorylation, Retinoblastoma

Mammalian G1 cyclins

Article Abstract:

G1 cyclins types C, D1 and E which were isolated through their potential to supplement conditionally defective CLN function in yeast are normally expressed during the G1 interval of the cell cycle in mammalian cells. The cyclins and their cyclin-dependent kinases (Cdks) are the integrators of the growth factor-mediated signals which drive the cell cycle. Cyclin D1 acts as a positive growth regulator, and cyclin E causes the early onset of DNA replication. Cyclin C level is maintained at a minimal level throughout the cell cycle.

Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint

Article Abstract:

The binding of cyclin A-kinase to the E2F-1 transcription factor removes the S phase arrest and inhibits the fibroblast transformation activity of E2F-1. This is probably due to the phosphorylation of DP-1, a heterodimeric partner of E2F-1, by the cyclin A-kinase bound to E2F-1. The suppression of the binding delays or arrests S phase progression, followed by regrowth or cell death. The control of E2F-1 by cyclin A-kinase is necessary for normal cell cycle progression, cell viability and fibroblast transformation.

Physiological aspects, Genetic regulation, Genetic transcription, Transcription (Genetics), Cellular control mechanisms, Cell regulation, Cooperative binding (Biochemistry)