Recombinant Human Cyclin D1 protein (GST tag N-Terminus + His tag N-Terminus)

General info

Function

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed : 1827756, PubMed : 1833066, PubMed : 19412162, PubMed : 33854235, PubMed : 8114739, PubMed : 8302605). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed : 1827756, PubMed : 1833066, PubMed : 19412162, PubMed : 8114739, PubMed : 8302605). Hypophosphorylates RB1 in early G(1) phase (PubMed : 1827756, PubMed : 1833066, PubMed : 19412162, PubMed : 8114739, PubMed : 8302605). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed : 1827756, PubMed : 1833066, PubMed : 19412162, PubMed : 8302605). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed : 15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed : 9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed : 16569215, PubMed : 18417529).

Sequence similarities

Belongs to the cyclin family. Cyclin D subfamily.

Post-translational modifications

Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex (PubMed:10766840, PubMed:17205132, PubMed:33854232, PubMed:33854235, PubMed:33854239). It also plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex following DNA damage (PubMed:19412162).. Ubiquitinated at Lys-269 by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-286 phosphorylation (PubMed:33854232, PubMed:33854235, PubMed:33854239). The DCX(AMBRA1) complex represents the major regulator of CCND1 stability during the G1/S transition (PubMed:33854232, PubMed:33854235, PubMed:33854239). Also ubiquitinated by the SCF(FBXO4) and Cul7-RING(FBXW8) ubiquitin-protein ligase complexes (PubMed:17205132). Following DNA damage it is ubiquitinated by the SCF(FBXO31) protein ligase complex (PubMed:19412162, PubMed:29279382). SCF(FBXO31) ubiquitination is dependent on Thr-286 phosphorylation (PubMed:10766840, PubMed:19412162, PubMed:29279382). Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner (PubMed:21952639). Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization (PubMed:19917254). Ubiquitinated by FBXO32 at Lys-58 via 'Lys27'-linked polyubiquitination; leading to its stabilization (PubMed:40307251).

Subcellular localisation

Nucleus