Disease relevance of CCNC

• The CCNC gene structure was also determined, and we have shown that it is deleted in a subset of acute lymphoblastic leukemias, including a patient sample containing a t(2;6)(p21;q15), with no apparent cytogenetic deletion [1].
• Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection [2].
• CONCLUSIONS: Amplification of the cyclin C gene was related to an unfavourable prognosis and high protein expression of cyclin A was associated with a better outcome in colon adenocarcinoma [3].
• We screened various cancer cell lines by quantitative PCR and found that the 1alpha,25(OH)2D3 inducibility of cyclin C mRNA expression, in relationship with the 24-hydroxylase (CYP24) gene, was best in MCF-7 human breast cancer cells [4].
• Furthermore, cyclin C expression was not affected by hypoxia [5].

Psychiatry related information on CCNC

• Cyclin C expression is involved in the pathogenesis of Alzheimer's disease [6].

High impact information on CCNC

• Cyclin C/cdk3 promotes Rb-dependent G0 exit [7].
• We have isolated a novel 87 kDa cyclin C-related protein (cyclin T) that interacts specifically with the transactivation domain of Tat [8].
• Cyclin C and E mRNAs accumulate periodically through the cell cycle, peaking at different times in G1 [9].
• The cdk8/cyclin C protein complex is also found in a number of mammalian Mediator-like protein complexes, which repress activated transcription independently of the CTD in vitro [10].
• Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo [11].

Biological context of CCNC

• Single-strand conformational polymorphism analysis of the remaining CCNC allele from patients with a deletion of one allele established that there were no further mutations within the exons or the flanking intronic sequences [1].
• This suggested that cyclin C might play a role in cell cycle control, but progress toward understanding the function of this cyclin has been hampered by the lack of information on a potential kinase partner [11].
• These results suggest either that haploinsufficiency of the cyclin C protein is sufficient to promote tumorigenesis or that the important tumor suppressor gene is linked to the CCNC locus [1].
• Here we show that a non-cdk8-associated cellular pool of cyclin C combines with cdk3 to stimulate pRb phosphorylation at S807/811 during the G0/G1 transition, and that this phosphorylation is required for cells to exit G0 efficiently [7].
• Furthermore, regulation of cell adhesion appears to be a feature unique to cyclin C, but not other G1 cyclins, E and D3, and its regulatory function is independent of CDK8 kinase activity [12].

Anatomical context of CCNC

• The present observations suggest different cellular functions of cyclin C in neurons and astrocytes in AD [6].
• Further role of Vitamin D is envisaged in identifying cyclin C as an important target for Vitamin D in cell-cycle regulation.Vitamin D at physiological concentration has been found to protect cell proteins and membranes against oxidative stress by inhibiting the peroxidative attack on membrane lipids [13].

Associations of CCNC with chemical compounds

• Immunoprecipitation of the approximately 2-MDa fraction with anti-Cdk8 antibody indicated that at least two classes of Mediator complexes occur, one containing CDK8 and cyclin C and one lacking this CDK-cyclin pair [14].
• Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter [4].
• The candidate human tumor suppressor gene cyclin C is a primary target of the anti-proliferative hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], but binding sites for the 1alpha,25(OH)2D3 receptor (VDR), so-called 1alpha,25(OH)2D3 response elements (VDREs), have not yet been identified in the promoter of this gene [4].
• Besides this, some genes were up-regulated, such as Integrin beta 8, DNA-PK, CSPCP, cyclin C etc [15].

Physical interactions of CCNC

• We have identified at least two distinct cyclin C/CDK8 containing complexes within the cell, a larger complex over 500 kD in size, that also contains the largest subunit of RNA polymerase II, and a smaller 170 kD species [16].
• In an article published recently in Cell, Ren and Rollins investigate mechanisms controlling the G0/G1 transition in quiescent cells and identify new cyclin C/Cdk3 complexes as key regulators of cell cycle reentry in human cells [17].

Other interactions of CCNC

• Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function [11].
• Unlike cyclin Ds and cyclin E, also identified in this screen, cyclin C has not been found to have a cell-cycle role in metazoa [18].
• To study the involvement of cyclins in cell-cycle progression, changes of mRNA levels for three G1 cyclins (cyclin C, D1 and E) and cyclin A were studied in a leukemia cell line, HEL cells, before and after incubation with 12-O-tetradecanoylphorbol-13-acetate (TPA) [19].

Analytical, diagnostic and therapeutic context of CCNC

• Consistent with the viability studies, the elevated TUNEL signal is reversed in cyclin C mutants [20].
• To characterize the molecular mechanisms, we analyzed 8.4 kb of the cyclin C promoter by using chromatin immunoprecipitation assays (ChIP) with antibodies against acetylated histone 4, VDR and its partner receptor, retinoid X receptor (RXR) [4].

References