Disease relevance of Ccnd3

• Finally, we found that cyclin D3 protein is expressed in a fraction of human goiters but it is strongly overexpressed in most follicular adenomas [1].
• Antiproliferative action of valproate is associated with aberrant expression and nuclear translocation of cyclin D3 during the C6 glioma G1 phase [2].

High impact information on Ccnd3

• Substantial evidence suggests that cyclin D1 plays a pivotal role in the control of the hepatocyte cell cycle in response to mitogenic stimuli, whereas the closely related protein cyclin D3 has not been extensively evaluated [3].
• In quiescent cells, cyclin D3 and cdk4 were cytoplasmatic, whereas cyclin D1 was nuclear [4].
• Compared with control animals, animals treated with 2-AAF showed increased levels of cdk 4 and cyclin D3 from 12 and 15 hours after PH, respectively, and altered cyclicity in cyclin D3 expression [5].
• In contrast, cyclin D3 expression coincides with podocyte differentiation and quiescence [6].
• Activation of endogenous (PRL) or transfected estrogen-responsive genes occurs at the same, higher concentrations of E2 required to promote cell survival, whereas stimulation of cyclin D3 expression and DNA synthesis occur at lower E2 concentrations [7].

Chemical compound and disease context of Ccnd3

• Exposure of C6 glioma to VPA induced a marked up-regulation of cyclin D3 and decreased expression of the proliferating cell nuclear antigen [2].

Biological context of Ccnd3

• D-type cyclins including cyclin D1, cyclin D2, and cyclin D3 are cell cycle regulators that promote progression through the early-to-mid G1 phase of the cell cycle [8].
• The increase in cyclin D3 expression occurred after the propylthiouracil-induced increase in TSH levels and preceded the burst of cell proliferation [1].
• We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland [1].
• Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition [1].
• To investigate the transcription initiation mechanism of the gene encoding cyclin D3, one of the major G1 cyclins to promote the G1/S transition, we cloned the 5' portion of rat cyclin D3 gene and analyzed the promoter region [9].

Anatomical context of Ccnd3

• Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in hyperproliferative diseases of the thyroid gland [1].
• At 28 hours, the activity of cdk4 in this nuclear subfraction decreased when cyclin D1 moved from this fraction to the nuclear matrix (NM) and the levels of cyclin D3 diminished [4].
• Immunoprecipitation confirmed a greater than 20-fold increase in the levels of cyclin D3 protein in the differentiated L6 myotubes as well as its association with a number of proteins [10].
• Immunohistochemistry demonstrated strong staining for cyclin D3 protein in the nuclei of the multinucleated myotubes from 4 independent myoblast cell lines; L6, L8, G8 and C2C12 [10].
• Cytoplasmic localization of cyclin D3 in seminiferous tubules during testicular development [11].

Associations of Ccnd3 with chemical compounds

• Cyclin D3 protein levels were higher in the thyrocytes from glands of propylthiouracil-treated rats compared with control animals [1].
• In contrast, cytochalasin D, lovastatin (a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor) and Y-27632 (a rho-kinase inhibitor) prevented both cyclin D3 expression and BrdU incorporation [12].
• Unlike glucocorticoid action, the effect of DES on thymocyte proliferation does not appear to be mediated by direct down regulation of cyclin D3 [13].
• The expression of the G1 markers c-Myc and cyclin D3 were unaffected by DEX treatment [14].
• Cyclin D3, important in cell cycle progression and Wilms tumor 1, related to cancer development, were also up-regulated in the vitamin E deficient animals [15].
• Mesangial cell cultures treated with poly(I:C) or tunicamycin in normal glucose media synthesized monocyte-adhesive hyaluronan matrices but with concurrent down-regulation of cyclin D3 [16].

Physical interactions of Ccnd3

• Western assays demonstrated, further, that cyclin D3 was complexed with the cyclin dependent-kinases, cdk2 and cdk4, in differentiated L6 cells [10].

Regulatory relationships of Ccnd3

• Dominant-negative FAK mutants prevented an ET-induced increase in cyclin D3 expression, but not D1 [12].
• Cyclin D1 was up-regulated in the mid-G1 phase (4-6 h) while cyclin D3 expression emerged only in late G1 (9-12 h) [2].
• Focal adhesion kinase mediates endothelin-induced cyclin D3 expression in rat cultured astrocytes [12].
• The TATA-less cyclin D3 gene is stimulated by prolactin (PRL) in rat Nb2 T-lymphocytes [17].

Other interactions of Ccnd3

• In contrast, cyclin D3 mRNA appears early in G1, remains constant in stimulated cells, but accumulates in unstimulated arrested cells, paralleling the cyclin-dependent kinase 4 mRNA expression [18].
• Cyclin D3 levels were not affected by TGF-beta 1 during G1 traverse [19].
• Addition of serum was followed by enhanced cyclin D1 expression, decreased p27(KIP1) levels, hyperphosphorylation of Rb protein, induction of cyclin A and cyclin D3 expression, and cell cycle progression into S phase [20].
• Many of the genes in this group have roles in cell division, such as cyclin B, cyclin D3, E2F-5, cdc 25B, polo-like kinase, and protein kinase C type III [21].
• The present study was undertaken to determine the precise localization of stathmin, a protein associated with microtubule dynamics, during decidualization in rat uterus and to compare it with that of cyclin D3 [22].

Analytical, diagnostic and therapeutic context of Ccnd3

• At 5 hours after hepatectomy, cyclin D3 and cdk4 began to move into the nucleus, and at 13 hours, they were mostly nuclear [4].
• Mobility shift assays identified proteins in Schwann cell nuclear extracts that formed stable complexes with the cyclin D3 CCAAT promoter element and were disrupted by anti-C/EBPbeta antibody [23].
• Interestingly, Western blot analysis of protein extracts from RVRT showed the induction of a new 40 kDa protein that cross-reacted with the cyclin D3 antibody [24].

References