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Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular
Baidehi Maiti1, Jing Li, Alain de Bruin
1Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and Department of Molecular Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Abstract:
The E2F transcription factor family plays a crucial and well established role in cell cycle progression. Deregulation of E2F activities in vivo leads to developmental defects and cancer. Based on current evidence in the field, mammalian E2Fs can be functionally categorized into either transcriptional activators (E2F1, E2F2, and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6, and E2F7). We have identified a novel E2F family member, E2F8, which is conserved in mice and humans and has its counterpart in Arabidopsis thaliana (E2Ls). Interestingly, E2F7 and E2F8 share unique structural features that distinguish them from other mammalian E2F repressor members, including the presence of two distinct DNA-binding domains and the absence of DP-dimerization, retinoblastoma-binding, and transcriptional activation domains. Similar to E2F7, overexpression of E2F8 significantly slows down the proliferation of primary mouse embryonic fibroblasts. These observations, together with the fact that E2F7 and E2F8 can homodimerize and are expressed in the same adult tissues, suggest that they may have overlapping and perhaps synergistic roles in the control of cellular proliferation.
Insights
Researchers identified a new E2F transcription factor, E2F8, crucial for cell cycle control. E2F8 and E2F7 may work together to regulate cell proliferation, impacting development and cancer.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The E2F transcription factor family is essential for cell cycle progression.
- Dysregulation of E2F activity is linked to developmental abnormalities and cancer.
- Mammalian E2Fs are classified as transcriptional activators or repressors.
Purpose of the Study:
- To identify and characterize novel members of the E2F transcription factor family.
- To investigate the structural and functional properties of the newly identified E2F8.
- To explore the potential roles of E2F8 in cellular proliferation and its relationship with other E2F family members.
Main Methods:
- Bioinformatic analysis to identify conserved E2F family members across species.
- Molecular cloning and characterization of the novel E2F8 gene.
- Overexpression studies in primary mouse embryonic fibroblasts to assess effects on cell proliferation.
- Analysis of structural features and dimerization capabilities of E2F7 and E2F8.
Main Results:
- A novel E2F family member, E2F8, conserved in mice and humans, was identified.
- E2F8 shares unique structural features with E2F7, including two DNA-binding domains and lacking DP-binding and transcriptional activation domains.
- Overexpression of E2F8 significantly inhibited the proliferation of mouse embryonic fibroblasts, similar to E2F7.
- E2F7 and E2F8 can homodimerize and are co-expressed in adult tissues.
Conclusions:
- E2F8 represents a novel member of the E2F transcription factor family with unique structural characteristics.
- E2F8 plays a role in the regulation of cellular proliferation.
- E2F7 and E2F8 likely possess overlapping or synergistic functions in controlling cell proliferation, potentially impacting developmental processes and cancer.
