Disease relevance of CCNY

• Structural similarity between the pocket region of retinoblastoma tumour suppressor and the cyclin-box [1].

High impact information on CCNY

• On cyclin A, it binds in a groove formed by conserved cyclin box residues [2].
• The cyclin box fold: protein recognition in cell-cycle and transcription control [3].
• The N-terminal cyclin box fold of cyclin E1 is similar to that of cyclin A and promotes identical changes in pCDK2 that lead to kinase activation [4].
• The specificity of the cyclin H molecule is provided mainly by two long helices which extend the cyclin fold at its N- and C-termini and pack together against the first repeat on the side opposite to the kinase [5].
• Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm [6].

Biological context of CCNY

• A novel cyclin gene was discovered by searching an expressed sequence tag database with a cyclin box profile [7].
• The N-terminal 272 residues of hCyclinT1, including the entire cyclin domains and the Tat.TAR recognition motif (TRM), that fully support Tat transactivation was used for panning, and of the five unique anti-hCyclinT1 sFvs that were obtained, three bound to the cyclin box domains and two bound to TRM [8].
• Our analysis demonstrates the existence of a number of islands of homology outside the cyclin box, and indicates candidate residues for phosphorylation [9].
• The cyclin box and C-terminus of cyclins A and E specify CDK activation and substrate specificity [10].
• Analysis of deletion mutants of glutathione-S-transferase (GST)-cyclin B2 mapped its binding domain for TGFbeta RII to the C-terminal and revealed a negative regulatory region immediately upstream of the cyclin box [11].

Anatomical context of CCNY

• Using a monoclonal antibody developed to a mouse trophectodermal carcinoma stem cell line E6496D lysate, we have identified the gene that encodes murine cyclin E. The cDNA contains a consensus cyclin box and a long 3' untranslated region and shares over 75% homology with human cyclin E cDNA [12].
• In addition, cyclin fold protein 1 variant A and pre-B-cell leukemia transcription factor 1 were lowly expressed in the non-metastatic cell line and were significantly upregulated in the metastatic cell line [13].

Other interactions of CCNY

• Our findings also indicate that the cyclin box in cyclin E mediates the interaction with cdk2 [14].
• A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the cell-cycle inhibitor p27(Kip1) [15].
• All three human D-type cyclin genes encode small (33-34 kDa) proteins that share an average of 57% identity over the entire coding region and 78% in the cyclin box [16].
• Protein binding and REF assays showed that the region of the cyclin box required for the interaction with CDK4 as well as C-terminal sequences determining protein stability were crucial for transformation [17].
• Moreover, the cyclin box of cyclin T1 and its immediate flanking region are largely responsible for the specific P-TEFb-Tat interaction [18].

Analytical, diagnostic and therapeutic context of CCNY

• Shoot meristem cells and dividing cells were marked from very early stages using in situ hybridization studies with Brostm, a Brassica homologue of the Arabidopsis SHOOTMERISTEMLESS (STM) gene, and a cyclin box-derived probe, Brocyc, respectively [19].
• In fact, although the amino acid sequence of Nck5a has little similarity to those of cyclins, recent experimental results obtained by site-directed mutagenesis studies have indicated that its activation domain, Nck5a*, may adopt a conformation of the cyclin-fold structure [20].
• Molecular cloning and antiserum development of cyclin box in the brown tide alga Aureococcus anophagefferens [21].
• We have demonstrated the presence of cyclin-box-containing polypeptides in dinoflagellates by immunoblotting using peptide-generated antibodies [22].

References