Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Identification of interaction partners and substrates of the cyclin A1-CDK2 complex.

The CDK2-associated cyclin A1 is essential for spermatogenesis and contributes to leukemogenesis. The detailed molecular functions of cyclin A1 remain unclear, since the molecular networks involving cyclin A1-CDK2 have not been elucidated. Here, we identified novel cyclin A1/CDK2 interaction partners in a yeast triple-hybrid approach. Several novel proteins (INCA1, KARCA1, and PROCA1) as well as the known proteins GPS2 (G-protein pathway suppressor 2), Ku70, receptor for activated protein kinase C1/guanine nucleotide-binding protein beta-2-like-1, and mRNA-binding motif protein 4 were identified as interaction partners. These proteins link the cyclin A1-CDK2 complex to diverse cellular processes such as DNA repair, signaling, and splicing. Interactions were confirmed by GST pull-down assays and co-immunoprecipitation. We cloned and characterized the most frequently isolated unknown gene, which we named INCA1 (inhibitor of CDK interacting with cyclin A1). The nuclear INCA1 protein is evolutionarily conserved and lacks homology to any known gene. This novel protein and two other interacting partners served as substrates for the cyclin A1-CDK2 kinase complex. Cyclin A1 and all interaction partners were highly expressed in testis with varying degrees of tissue specificity. The highest expression levels were observed at different time points during testis maturation, whereas expression levels in germ cell cancers and infertile testes decreased. Taken together, we identified testicular interaction partners of the cyclin A1-CDK2 complex and studied their expression pattern in normal organs, testis development, and testicular malignancies. Thereby, we establish a new basis for future functional analyses of cyclin A1. We provide evidence that the cyclin A1-CDK2 complex plays a role in several signaling pathways important for cell cycle control and meiosis.

Pubmed ID: 15159402 RIS Download

Mesh terms: Alternative Splicing | Amino Acid Sequence | Animals | Base Sequence | Blotting, Northern | CDC2-CDC28 Kinases | COS Cells | Carrier Proteins | Cell Cycle | Cercopithecus aethiops | Cyclin A | Cyclin A1 | Cyclin-Dependent Kinase 2 | DNA Repair | Gene Expression | Gene Library | Glutathione Transferase | Humans | Immunosorbent Techniques | Infertility, Male | Male | Meiosis | Molecular Sequence Data | Phosphoproteins | Phosphorylation | RNA Splicing | RNA, Messenger | Recombinant Fusion Proteins | Reverse Transcriptase Polymerase Chain Reaction | Sequence Homology | Signal Transduction | Testicular Neoplasms | Testis | Transfection

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

Associated grants


BioGRID (Data, Interactions)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.