Cyclin A2

Cyclin A2 is a protein belonging to the cyclin family, a group of proteins that regulate the cell cycle. Specifically, Cyclin A2 plays a crucial role in both S phase (DNA replication) and early mitosis (cell division).

Function:

Cyclin A2 primarily functions by activating cyclin-dependent kinases (CDKs). When Cyclin A2 binds to and activates its CDK partner, primarily CDK2 and CDK1, it forms a complex that phosphorylates target proteins necessary for cell cycle progression.

• S Phase: Cyclin A2-CDK2 activity is essential for the initiation and completion of DNA replication. It phosphorylates proteins involved in the assembly of the pre-replication complex (pre-RC) at replication origins, triggering DNA synthesis.

• Early Mitosis: Cyclin A2-CDK1 activity is required for the proper entry into and progression through early mitosis. It phosphorylates target proteins involved in chromosome condensation, spindle formation, and nuclear envelope breakdown.

Regulation:

The levels and activity of Cyclin A2 are tightly regulated to ensure the correct timing of cell cycle events. Regulation occurs through various mechanisms, including:

• Transcriptional Control: The transcription of the CCNA2 gene (encoding Cyclin A2) is cell cycle regulated.

• Protein Stability: Cyclin A2 protein levels fluctuate throughout the cell cycle, with a peak during S and G2 phases. Protein stability is regulated by ubiquitination and proteasomal degradation.

• CDK Inhibitors (CKIs): CKIs can bind to Cyclin A2-CDK complexes, inhibiting their activity.

• Phosphorylation: Phosphorylation of Cyclin A2 or its CDK partner can either activate or inhibit the complex's activity.

Clinical Significance:

Aberrant expression or regulation of Cyclin A2 has been implicated in various cancers. Overexpression of Cyclin A2 can promote uncontrolled cell proliferation, contributing to tumorigenesis. Cyclin A2 is therefore a potential therapeutic target in cancer treatment.

See Also:

• Cyclins
• Cyclin-Dependent Kinases (CDKs)
• Cell Cycle
• Mitosis
• DNA Replication