The E2F transcription regulator family members are known to be transcriptional activators or repressors, playing important roles in regulating cell cycle, DNA synthesis, and apoptosis. Activators such as E2F1, E2F2, and E2F3a promote and help carry out the cell cycle, while repressors like E2F3b and E2F4-8 inhibit the cell cycle, in which redundancy and heterodimerization among the family members were observed. The balance between E2F repressors and activators regulates the cell cycle progression, as when activator E2F family members are repressed, repressors become active to inhibit E2F target genes. E2F TFs bind to the TTTCCCGC consensus binding site in the target promoter sequence. Most E2F have a pocket protein binding domain, allowing pocket proteins to bind to phosphorylated E2F proteins blocking the transcription activation activity or recruiting repression complexes to silence target genes to promote E2F repression function. Nonetheless, E2F6, E2F7, and E2F8 do not have pocket protein binding sites, and their mechanism for gene silencing is unclear. Among E2F transcriptional targets are cyclins, CDKs, checkpoint regulators, DNA repair, and replication proteins.
Aberrant E2F transcription has been identified in many human malignancies, where the E2F transcription factors have been shown to promote the growth and invasion of tumor cells. Mechanistically, dysregulated E2Fs can activate or silence oncogenes or tumor suppressors at multiple levels, including transcriptional level, post-transcriptional level, translational level, protein-protein interaction level, and transcriptional activity level, further causing the carcinogenesis in human malignancies. Moreover, E2F control of miRNAs is likely to play multiple roles in cell proliferation during cancer development. However, the specific functions and intricate machinery of all eight E2Fs and their variants in human cancer remain unclear in many aspects. Members of the E2F family have been suggested to be diagnostic and prognostic biomarkers for certain cancers. Enhanced E2F activity was also proposed as a key mechanism for chemoradiotherapy drug resistance. Recently, anti-cancer drugs targeting E2Fs have been transferred from preclinical to clinical application.
This Research Topic welcomes submissions of Original Research Articles and Reviews highlighting the role of E2Fs in tumorigenesis, progress diagnostic, prognostic potential, and therapy of cancer patients. Topics of interest include, but are not limited to:
- novel functions of the E2F family in tumor progression
- therapeutic approaches that target E2F family members
- deregulation of E2F regulatory pathways in cancer
- development of biomarkers for tumor prognosis and therapeutic progress
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The E2F transcription regulator family members are known to be transcriptional activators or repressors, playing important roles in regulating cell cycle, DNA synthesis, and apoptosis. Activators such as E2F1, E2F2, and E2F3a promote and help carry out the cell cycle, while repressors like E2F3b and E2F4-8 inhibit the cell cycle, in which redundancy and heterodimerization among the family members were observed. The balance between E2F repressors and activators regulates the cell cycle progression, as when activator E2F family members are repressed, repressors become active to inhibit E2F target genes. E2F TFs bind to the TTTCCCGC consensus binding site in the target promoter sequence. Most E2F have a pocket protein binding domain, allowing pocket proteins to bind to phosphorylated E2F proteins blocking the transcription activation activity or recruiting repression complexes to silence target genes to promote E2F repression function. Nonetheless, E2F6, E2F7, and E2F8 do not have pocket protein binding sites, and their mechanism for gene silencing is unclear. Among E2F transcriptional targets are cyclins, CDKs, checkpoint regulators, DNA repair, and replication proteins.
Aberrant E2F transcription has been identified in many human malignancies, where the E2F transcription factors have been shown to promote the growth and invasion of tumor cells. Mechanistically, dysregulated E2Fs can activate or silence oncogenes or tumor suppressors at multiple levels, including transcriptional level, post-transcriptional level, translational level, protein-protein interaction level, and transcriptional activity level, further causing the carcinogenesis in human malignancies. Moreover, E2F control of miRNAs is likely to play multiple roles in cell proliferation during cancer development. However, the specific functions and intricate machinery of all eight E2Fs and their variants in human cancer remain unclear in many aspects. Members of the E2F family have been suggested to be diagnostic and prognostic biomarkers for certain cancers. Enhanced E2F activity was also proposed as a key mechanism for chemoradiotherapy drug resistance. Recently, anti-cancer drugs targeting E2Fs have been transferred from preclinical to clinical application.
This Research Topic welcomes submissions of Original Research Articles and Reviews highlighting the role of E2Fs in tumorigenesis, progress diagnostic, prognostic potential, and therapy of cancer patients. Topics of interest include, but are not limited to:
- novel functions of the E2F family in tumor progression
- therapeutic approaches that target E2F family members
- deregulation of E2F regulatory pathways in cancer
- development of biomarkers for tumor prognosis and therapeutic progress
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.