E2F8

E2F8 is a member of the E2F transcription factor family, encoded by the human E2F8 gene located on chromosome 18p11.21. It functions predominantly as a transcriptional repressor and plays a key role in the regulation of the cell cycle, particularly during the G1/S transition. E2F8 forms heterodimers with retinoblastoma protein (Rb) and its related proteins, binding to DNA sequences in promoter regions of genes involved in DNA replication and cell cycle progression. Its activity is modulated by phosphorylation, which decreases its affinity for E2F-responsive elements and allows transcriptional activation of target genes by other E2F family members.

Expression of E2F8 is tissue‑specific, with high levels detected in proliferating cells such as embryonic tissues, hematopoietic progenitors, and certain cancer cell lines. During development, E2F8 helps maintain stem cell populations and ensures proper cell proliferation rates. In differentiated tissues, its expression is usually low, reflecting its role in cell cycle control rather than terminal differentiation.

Aberrant regulation of E2F8 has been implicated in oncogenesis. Overexpression or genomic amplification of E2F8 is observed in several tumor types, including breast, ovarian, and colorectal cancers, where it contributes to uncontrolled proliferation and tumor progression. Loss-of-function mutations and reduced expression of E2F8 have also been associated with developmental disorders involving growth defects and impaired cellular proliferation.

Research continues to delineate the full spectrum of E2F8 target genes and its interaction with other cell cycle regulators, offering potential avenues for therapeutic intervention in diseases characterized by dysregulated proliferation.