Pathway
G1/S-Specific Transcription
The E2F family of transcription factors regulate the transition from the G1 to the S phase in the cell cycle. E2F activity is regulated by members of the retinoblastoma protein (pRb) family, resulting in the tight control of the expression of E2F-responsive genes. Phosphorylation of pRb by cyclin D:CDK complexes releases pRb from E2F, inducing E2F-targeted genes such as cyclin E.
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E2F1 binds to E2F binding sites on the genome activating the synthesis of the target proteins. For annotation purposes, the reactions regulated by E2F1 are grouped under this pathway and information about the target genes alone are displayed for annotation purposes.
Cellular targets for activation by E2F1 include thymidylate synthase (TYMS), Rir2 (RRM2), Dihydrofolate reductase (DHFR), Cdc2 (CDK1), Cyclin A1 (CCNA1), CDC6, CDT1, CDC45, Cyclin E (CCNE1), Emi1 (FBXO5), and ORC1. The activation of TK1 (Dnk1) and CDC25A by E2F1 is conserved in Drosophila.
RRM2 protein is involved in dNTP level regulation and activation of this enzyme results in higher levels of dNTPs in anticipation of S phase. E2F activation of RRM2 has been shown also in Drosophila by Duronio and O'Farrell (1994). E2F1 activation of CDC45 is shown in mouse cells by using human E2F1 construct. Cyclin E is also transcriptionally regulated by E2F1. Cyclin E protein plays important role in the transition of G1 in S phase by associating with CDK2. E2F1-mediated activation of PCNA has been demonstrated in Drosophila and in some human cells by using recombinant adenovirus constructs. E2F1-mediated activation of the DNA polymerase alpha subunit p180 (POLA1) has been demonstrated in some human cells. It has also been demonstrated in Drosophila by Ohtani and Nevins (1994). It has been observed in Drosophila that E2F1 induced expression of Orc1 stimulates ORC1 6 complex formation and binding to the origin of replication. ORC1 6 recruit CDC6 and CDT1 that are required to recruit the MCM2 7 replication helicases. E2F1 regulation incorporates a feedback mechanism wherein Geminin (GMNN) can inhibit MCM2 7 recruitment of ORC1 6 complex by interacting with CDC6/CDT1. The activation of CDC25A and TK1 (Dnk1) by E2F1 has been inferred from similar events in Drosophila (Duronio RJ and O'Farrell 1994; Reis and Edgar 2004). E2F1 activates string (CDC25) that in turn activates the complex of Cyclin B and CDK1. A similar phenomenon has been observed in mouse NIH 3T3 cells and in Rat1 cells.
What the reference databases state
Statements
28 statements
28 statements · 1 reference database · Subject: G1/S-Specific Transcription · Sources: Reactome
- CCNA1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- CCNE1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- CDC45 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- CDC6 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- CDK1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- CDT1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- DHFR participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- E2F1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- E2F4 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- E2F5 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- E2F6 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- FBXO5 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
Show the remaining 16
- HDAC1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- LIN37 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- LIN52 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- LIN54 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- LIN9 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- ORC1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- PCNA participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- POLA1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- RBBP4 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- RBL1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- RBL2 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- RRM2 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- TFDP1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- TFDP2 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- TK1 participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only
- TYMS participates in G1/S-Specific TranscriptionProteinReactome R-HSA-69205Inferred only