CCND1

Cyclin D1 is a protein that in humans is encoded by the CCND1 gene.

Cyclin D1

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 G1/S transition. 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 G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.

Cell division Source: UniProtKB-KW
Cellular response to DNA damage stimulus Source: UniProtKB
Cytokine-mediated signaling pathway Source: Reactome
Endoplasmic reticulum unfolded protein response Source: Ensembl
Fat cell differentiation Source: Ensembl
G1/S transition of mitotic cell cycle Source: UniProtKB
Lactation Source: Ensembl
Leydig cell differentiation Source: Ensembl
Liver regeneration Source: Ensembl
Mammary gland alveolus development Source: Ensembl
Mammary gland epithelial cell proliferation Source: Ensembl
Mitotic cell cycle phase transition Source: GO_Central
Mitotic G1 DNA damage checkpoint Source: UniProtKB
Negative regulation of cell cycle arrest Source: UniProtKB
Negative regulation of epithelial cell differentiation Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of cell cycle Source: Reactome
Positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
Positive regulation of G1/S transition of mitotic cell cycle Source: GO_Central
Positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
Positive regulation of mammary gland epithelial cell proliferation Source: Ensembl
Positive regulation of protein phosphorylation Source: BHF-UCL
Re-entry into mitotic cell cycle Source: Ensembl
Regulation of cyclin-dependent protein serine/threonine kinase activity Source: GO_Central
Regulation of transcription initiation from RNA polymerase II promoter Source: Reactome
Response to calcium ion Source: Ensembl
Response to corticosterone Source: Ensembl
Response to drug Source: UniProtKB
Response to estradiol Source: Ensembl
Response to estrogen Source: Ensembl
Response to ethanol Source: Ensembl
Response to iron ion Source: Ensembl
Response to leptin Source: UniProtKB
Response to magnesium ion Source: Ensembl
Response to organonitrogen compound Source: Ensembl
Response to UV-A Source: BHF-UCL
Response to vitamin E Source: Ensembl
Response to X-ray Source: Ensembl
Wnt signaling pathway Source: Ensembl

Cytoplasm; Nucleus; Nucleus membrane. Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members.

A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle.
A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer.
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.

Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage. It probably plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex.
Ubiquitinated, primarily as 'Lys-48'-linked polyubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4 and CRYAB. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. SCF-type ubiquitination is dependent on Thr-286 phosphorylation (By similarity). Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner. Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization.