Figure 1
Schematic representation of cyclin D1 (top) and cyclin D1b (bottom) regulatory sequences. Cyclin D1 stability is regulated by various mechanisms. The n-terminal region has recently been shown to be important for regulating stability [27]. (?) The mechanisms that regulate cyclin D1 stability via the n-terminal remain to be clearly defined. The RxxL motif is required for APC (Anaphase Promoting Complex) mediated degradation following genotoxic insult [48]. GSK3β phosphorylates threonine residue 286 (T286) and regulates cyclin D1 nuclear export and stability [5, 40]. p38SAPK2 and ERK2 have also been shown to regulate cyclin D1 stability by phosphorylating T286 [9, 49, 114]. The threonine 288 residue (T288) has also been shown to regulate cyclin D1 stability. Phosphorylation of T288 is mediated by the mirk/Dyrk 1b kinase [47]. In cyclin D1b, regulatory motifs and residues within the c-terminal region downstream of residue 240 are replaced by sequence from intron 4 of the CCND1 gene [62, 63]. Adapted from Knudsen, 2006 [13, 65].