Phospho-Cyclin D3 (Thr283) (E1V6W) Rabbit mAb #53966

Activity of the cyclin-dependent kinases CDK4 and CDK6 is regulated by T-loop phosphorylation, by the abundance of their cyclin partners (the D-type cyclins), and by association with CDK inhibitors of the Cip/Kip or INK family of proteins (1). The inactive ternary complex of cyclin D/CDK4 and p27 Kip1 requires extracellular mitogenic stimuli for the release and degradation of p27 concomitant with a rise in cyclin D levels to affect progression through the restriction point and Rb-dependent entry into S-phase (2). The active complex of cyclin D/CDK4 targets the retinoblastoma protein for phosphorylation, allowing the release of E2F transcription factors that activate G1/S-phase gene expression (3). Levels of cyclin D protein drop upon withdrawal of growth factors through downregulation of protein expression and phosphorylation-dependent degradation (4).
Although the D-type cyclins are not fully redundant, cyclin D3, like D1, plays a prominent role in differentiation and proliferation, which correlates with higher expression levels of cyclin D3 in various cancers (5). Burkitt lymphoma can carry mutations in the cyclin D3 gene that can affect phosphorylation at Thr283, stability of the protein, and cell cycle progression (6).