Activation of E2F1 target genes at G1/S

Stable Identifier
R-HSA-539107
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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) (DeGregori et al. 1995), Rir2 (RRM2) (DeGregori et al. 1995, Giangrande et al. 2004), Dihydrofolate reductase (DHFR) (DeGregori et al. 1995, Wells et al. 1997, Darbinian et al. 1999), Cdc2 (CDK1) (Furukawa et al. 1994, DeGregori et al. 1995, Zhu et al. 2004), Cyclin A1 (CCNA1) (DeGregori et al. 1995, Liu et al. 1998), CDC6 (DeGregori et al. 1995, Yan et al. 1998; Ohtani et al. 1998), CDT1 (Yoshida and Inoue 2004), CDC45 (Arata et al. 2000), Cyclin E (CCNE1) (Ohtani et al. 1995), Emi1 (FBXO5) (Hsu et al. 2002), and ORC1 (Ohtani et al. 1996, Ohtani et al. 1998). The activation of TK1 (Dnk1) (Dou et al. 1994, DeGregori et al. 1995, Giangrande et al. 2004) and CDC25A (DeGregori et al. 1995, Vigo et al. 1999) by E2F1 is conserved in Drosophila (Duronio and O'Farrell 1994, Reis and Edgar 2004).
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 (Arata et al. 2000). 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 (Ohtani et al. 1996). E2F1-mediated activation of PCNA has been demonstrated in Drosophila (Duronio and O'Farrell 1994) and in some human cells by using recombinant adenovirus constructs (DeGregori et al. 1995). 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 (Asano and Wharton 1999). 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.

Literature References
PubMed ID Title Journal Year
8943353 Expression of the HsOrc1 gene, a human ORC1 homolog, is regulated by cell proliferation via the E2F transcription factor Mol Cell Biol 1996
9778043 Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F. Oncogene 1998
8114698 Functional properties of a Drosophila homolog of the E2F1 gene Mol Cell Biol 1994
8618861 Regulation of the cyclin E gene by transcription factor E2F1 Proc Natl Acad Sci U S A 1995
10228158 E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila EMBO J 1999
14990995 Regulation of Geminin and Cdt1 expression by E2F transcription factors Oncogene 2004
9020173 Accumulation of E2F-4.DP-1 DNA binding complexes correlates with induction of dhfr gene expression during the G1 to S phase transition J. Biol. Chem. 1997
8050359 Developmental control of a G1-S transcriptional program in Drosophila Development 1994
9662327 A new model of cell cycle-regulated transcription: repression of the cyclin A promoter by CDF-1 and anti-repression by E2F Oncogene 1998
11988738 E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1) Nat Cell Biol 2002
15510213 E2Fs link the control of G1/S and G2/M transcription EMBO J. 2004
7929342 The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells J. Biol. Chem. 1994
15084262 Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing Cell 2004
15014447 Combinatorial gene control involving E2F and E Box family members EMBO J. 2004
8288595 G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter J. Biol. Chem. 1994
10454584 CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase Mol Cell Biol 1999
10597240 Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1 Oncogene 1999
10692433 Cdk2-dependent and -independent pathways in E2F-mediated S phase induction J Biol Chem 2000
7623816 Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes Mol Cell Biol 1995
9520412 Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells. Proc Natl Acad Sci U S A 1998
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