Recombinded human Cyclin D1 protein, N-His (重组蛋白) | Bioss

CCND1

G1/S-specific cyclin-D1

Interacts with FBXO4. Interacts witheither CDK4 or CDK6 protein kinase to form a serine/threoninekinase holoenzyme complex. The cyclin subunit imparts substratespecificity to the complex. Component of the ternary complexCCND1/CDK4/CDKN1B required for nuclear translocation and modulationof CDK4-mediated kinase activity. Interacts directly with CDKN1B.Interacts with UHRF2; the interaction ubiquitinates CCND1 andappears to occur independently of phosphorylation. Can form similarcomplexes with either CDKN1A or CDKN2A. Interacts with USP2.

Nucleus. Cytoplasm. Membrane. Note=CyclinD-CDK4 complexes accumulate at the nuclear membrane and are thentranslocated to the nucleus through interaction with KIP/CIP familymembers.

Phosphorylation at Thr-286 by MAP kinases is required forubiquitination and degradation following DNA damage. It probablyplays an essential role for recognition by the FBXO31 component ofSCF (SKP1-cullin-F-box) protein ligase complex.
Ubiquitinated, primarily as 'Lys-48'-linkedpolyubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-boxprotein) ubiquitin-protein ligase complex containing FBXO4 andCRYAB. 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 (Bysimilarity). Ubiquitinated also by UHRF2 apparently in aphosphorylation-independent manner. Ubiquitination leads to itsdegradation and G1 arrest. Deubiquitinated by USP2; leading to itsstabilization.

Note=A chromosomal aberration involving CCND1 may be acause of B-lymphocytic malignancy, particularly mantle-celllymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulingene regions. Activation of CCND1 may be oncogenic by directlyaltering progression through the cell cycle.
Note=A chromosomal aberration involving CCND1 may be acause of parathyroid adenomas. Translocation t(11;11)(q13;p15) withthe parathyroid hormone (PTH) enhancer.
Defects in CCND1 are a cause of multiple myeloma (MM)[MIM:254500]. MM is a malignant tumor of plasma cells usuallyarising in the bone marrow and characterized by diffuse involvementof the skeletal system, hyperglobulinemia, Bence-Jones proteinuriaand anemia. Complications of multiple myeloma are bone pain,hypercalcemia, renal failure and spinal cord compression. Theaberrant antibodies that are produced lead to impaired humoralimmunity and patients have a high prevalence of infection.Amyloidosis may develop in some patients. Multiple myeloma is partof a spectrum of diseases ranging from monoclonal gammopathy ofunknown significance (MGUS) to plasma cell leukemia. Note=Achromosomal aberration involving CCND1 is found in multiplemyeloma. Translocation t(11;14)(q13;q32) with the IgH locus.

Belongs to the cyclin family. Cyclin D subfamily.

Regulatory component of the cyclin D1-CDK4 (DC) complexthat phosphorylates and inhibits members of the retinoblastoma (RB)protein family including RB1 and regulates the cell-cycle duringG(1)/S transition. Phosphorylation of RB1 allows dissociation ofthe transcription factor E2F from the RB/E2F complex and thesubsequent transcription of E2F target genes which are responsiblefor the progression through the G(1) phase. Hypophosphorylates RB1in early G(1) phase. Cyclin D-CDK4 complexes are major integratorsof various mitogenenic and antimitogenic signals. Also substratefor SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent mannerand repressing its transcriptional activity. Component of theternary complex, cyclin D1/CDK4/CDKN1B, required for nucleartranslocation and activity of the cyclin D-CDK4 complex.