Disease relevance of Ccna1

• Increased cyclin A and decreased cyclin D levels in adenovirus 5 E1A-transformed rodent cell lines [1].
• CONCLUSION: Our data indicates that NO released from cardiomyocytes under condition of ischemia/reperfusion exerts an antiapoptotic effect by modulating cyclin A-associated kinase activity via p21(cip1/waf1) accumulation [2].

High impact information on Ccna1

• The ectopic expression of cyclin E restored cyclin A expression and drove the PSM-RB expressing cells into S phase [3].
• Role of c-fos and E2F in the induction of cyclin A transcription and vascular smooth muscle cell proliferation [4].
• Moreover, c-fos overexpression in serum-starved VSMCs results in the induction of cyclin A promoter activity in a CRE-dependent manner, and increased binding of endogenous c-fos protein to the cyclin A CRE precedes the onset of DNA replication in VSMCs induced by serum in vitro and by angioplasty in vivo [4].
• Downregulation of cyclin-dependent kinase 2 activity and cyclin A promoter activity in vascular smooth muscle cells by p27(KIP1), an inhibitor of neointima formation in the rat carotid artery [5].
• SNP and SNAP also repress the mitogen-stimulated activation of the cyclin A promoter [6].

Chemical compound and disease context of Ccna1

• Nitric oxide inhibits ischemia/reperfusion-induced myocardial apoptosis by modulating cyclin A-associated kinase activity [2].

Biological context of Ccna1

• Further examination revealed that cyclin A continued to be ubiquitinated by the anaphase promoting complex (APC) and to be degraded by the proteasome [7].
• The addition of SNP or SNAP to VSMC cultures at the time of serum stimulation abrogates the induction of cdk2 activity without suppressing protein levels of cdk2 or cyclin E. These NO donors block serum-stimulated upregulation of cyclin A mRNA and protein and repress the serum induction of cyclin A promoter activity in VSMCs [6].
• In contrast, expression of cyclin E, cyclin A, and Rb phosphorylation were delayed when quiescent c-myc heterozygous cells were stimulated to enter the cell cycle [8].
• The downstream effector of c-Myc is cyclin A, whose ectopic expression in c-myc(-/-) cells rescues the apoptosis defect [9].
• The kinetics of the G(2) response indicate that the induction of cyclin A and the concomitant activation of Cdk2 represent an early step during commitment to apoptosis [9].

Anatomical context of Ccna1

• Extracellular ATP induces anchorage-independent expression of cyclin A and rescues the transformed phenotype of a ras-resistant mutant cell line [10].
• ATP does not induce adhesion-independent expression of cyclin A in ER-1-2 or control rat fibroblasts that do not express Ras, indicating a requirement for additional Ras-regulated signals for expression of this gene; one such signal may lead to phosphorylation of the retinoblastoma protein, pRB, and related proteins [10].
• Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A [11].
• Therefore, we assessed the expression of the cytoplasmic proteins Bax and Bcl-2, respectively a promoter and an inhibitor of apoptosis, and the expression of cyclin A, a nuclear protein that induces proliferation of smooth muscle cells [12].
• Cell growth arrest in confluent astrocytes was found to be correlated with increased expression of CKI p21, resulting in inhibition of D-type cyclin-associated pRB phosphorylation and cyclin A expression [13].

Associations of Ccna1 with chemical compounds

• Nitric oxide-induced downregulation of Cdk2 activity and cyclin A gene transcription in vascular smooth muscle cells [6].
• Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities [11].
• These effects were independent of a cyclic AMP response element and conferred by the proximal 150 nucleotides of the cyclin A promoter [14].
• The cdk2 gene was induced in late G1 and cdc2 and cyclin A genes at the G1/S boundary in both serum-stimulated and dex-treated cells [15].
• Western blot showed loss of nuclear as well as cytoplasmic cyclin A and cyclin B protein after 2-AAF treatment, while the Rb protein level was markedly increased during G1 [16].

Regulatory relationships of Ccna1

• Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position [17].
• Here we report that CTGF induces this S-phase entry by upregulating cyclin A levels [18].
• We hypothesize that IFN-gamma inhibits cyclin A transcription by modifying co-activators or general transcription factors within the complex that drives transcription of the cyclin A gene [19].

Other interactions of Ccna1

• The transfer of serum-exposed IEC18 cells from adherent cultures to suspension cultures results in a rapid down-regulation of expression of cyclin D1 and cyclin A proteins as well as in retinoblastoma protein dephosphorylation [20].
• Taken together, these results suggest that cyclin A is a target of c-Jun and is necessary but not sufficient for c-Jun-induced anchorage-independent growth [21].
• The decrease in RB expression and phosphorylation, which is essential in triggering DNA synthesis and Cyclin A expression, leads to a deficiency in transcriptionally active E2F complex formation after hepatectomy [22].
• Expressed wild-type, but not mutant, CLS peptides localized on the centrosome, prevented endogenous cyclin E and cyclin A from localizing to the centrosome, and inhibited DNA synthesis [23].
• Systolic blood pressure was directly correlated (P < 0.01) with Bcl-2 and cyclin A in SHR [12].

Analytical, diagnostic and therapeutic context of Ccna1

• Here we investigated the transcriptional regulation of the cyclin A gene, a key positive regulator of S phase that is induced after angioplasty [4].
• Gel shift immunoassays show that CDP/cut forms a proliferation-specific protein/DNA complex in conjunction with cyclin A and p107, a member of the retinoblastoma protein family of tumor suppressors [24].
• Cyclin D1 and cyclin A were expressed at 24 to 48 h after reperfusion [25].
• Consequently there is a marked increase in expression (Western blot analysis, immunostaining) of cyclin A and CDK2 [26].
• We demonstrate that TCDD treatment significantly increases cyclin D2 and cyclin A protein levels and show by immunofluorescence that these proteins accumulate in the nucleus [27].

References