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)

Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex (PubMed:19237565, PubMed:8114739). The cyclin subunit imparts substrate specificity to the complex (PubMed:19237565, PubMed:20399237, PubMed:8302605, PubMed:9106657). Component of the ternary complex CCND1/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity (PubMed:9106657).

Interacts directly with CDKN1B (By similarity). Can form similar complexes with either CDKN1A or CDKN2A (By similarity). Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears to occur independently of phosphorylation (PubMed:21952639).

Interacts with USP2 (PubMed:19917254). Interacts (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity (PubMed:16569215, PubMed:18417529, PubMed:19124461). Interacts with CDK4; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression (PubMed:19124461).

Interacts with FBXO32; this interaction mediates CCND1 stabilization via 'Lys-27'-linked polyubiquitination (PubMed:40307251)

• Unknown disease
• Unknown disease
• Multiple myeloma (MM)

  A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection.

  Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia.