Cyclin E2

Cyclin E2

Cyclin E2 is a member of the cyclin family, which is a group of proteins that play a crucial role in regulating the cell cycle. Cyclins function as regulatory subunits that activate cyclin-dependent kinases (CDKs), and Cyclin E2 specifically associates with CDK2 to control the transition from the G1 phase to the S phase of the cell cycle.

Structure and Function

Cyclin E2 is structurally similar to Cyclin E1, sharing a significant degree of sequence homology. Both Cyclin E1 and Cyclin E2 bind to CDK2, but they have distinct expression patterns and regulatory mechanisms. Cyclin E2 is encoded by the CCNE2 gene, which is located on chromosome 8q22.1 in humans.

The primary function of Cyclin E2 is to regulate the G1/S transition in the cell cycle. It does this by forming a complex with CDK2, which then phosphorylates target proteins that are necessary for the initiation of DNA replication. This phosphorylation activity is crucial for the progression of cells from the G1 phase, where cells grow and prepare for DNA replication, to the S phase, where DNA synthesis occurs.

Expression and Regulation

Cyclin E2 expression is tightly regulated during the cell cycle. It is typically expressed at low levels during the G0 and early G1 phases, with expression peaking at the G1/S transition. The regulation of Cyclin E2 involves multiple mechanisms, including transcriptional control, protein stability, and degradation.

The transcription of CCNE2 is regulated by E2F transcription factors, which are themselves controlled by the retinoblastoma protein (pRB) pathway. When pRB is phosphorylated, E2F is released and can activate the transcription of Cyclin E2, among other genes.

Cyclin E2 is also subject to ubiquitin-mediated degradation, which is a key mechanism for controlling its levels and activity. The SCF complex (Skp, Cullin, F-box containing complex) targets Cyclin E2 for degradation via the ubiquitin-proteasome pathway, ensuring that its activity is restricted to the appropriate phase of the cell cycle.

Clinical Significance

Dysregulation of Cyclin E2 has been implicated in various cancers. Overexpression of Cyclin E2 can lead to uncontrolled cell proliferation, a hallmark of cancer. Studies have shown that Cyclin E2 is overexpressed in breast cancer, ovarian cancer, and other malignancies. This overexpression is often associated with poor prognosis and resistance to certain therapies.

Cyclin E2, along with Cyclin E1, is being studied as a potential biomarker for cancer diagnosis and prognosis. Additionally, targeting the Cyclin E2/CDK2 complex is being explored as a therapeutic strategy in cancers where Cyclin E2 is dysregulated.

See Also

• Cyclin E1
• Cyclin-dependent kinase
• Cell cycle
• Ubiquitin-proteasome pathway

References

• Hwang, H.C., & Clurman, B.E. (2005). Cyclin E in normal and neoplastic cell cycles. Oncogene, 24(17), 2776-2786.
• Caldon, C.E., & Musgrove, E.A. (2010). Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer. Cell Division, 5, 2.