Search results for TK1

Showing 13 results out of 13

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Protein (1 results from a total of 1)

TK1

Identifier: R-HSA-73500
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: TK1: P04183

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8954007
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000167900

Complex (3 results from a total of 3)

Identifier: R-HSA-73501
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8961992
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-NUL-8963658
Species: Mus musculus, Homo sapiens
Compartment: nucleoplasm

Reaction (6 results from a total of 6)

Identifier: R-NUL-9616935
Species: Mus musculus, Homo sapiens
Compartment: nucleoplasm
Transcription of the mouse Tk1 gene, encoding thymidine kinase, is directly stimulated by human E2F1 (Dou et al. 1994).
Identifier: R-NUL-8963657
Species: Homo sapiens, Mus musculus
Compartment: nucleoplasm
Human E2F1 binds to E2F binding sites in the promoter of the mouse Tk1 gene, encoding thymidine kinase (Dou et al. 1994).
Identifier: R-HSA-8961991
Species: Homo sapiens
Compartment: nucleoplasm
E2F1 binds to E2F binding sites in the promoter of the TK1 gene, encoding thymidine kinase (Dou et al. 1994, DeGregori et al. 1995, Giangrande et al. 2004).
Identifier: R-HSA-8962039
Species: Homo sapiens
Compartment: nucleoplasm
E2F1 directly stimulates transcription of the TK1 gene, encoding thymidine kinase (Dou et al. 1994, DeGregori et al. 1995, Giangrande et al. 2004).
Identifier: R-HSA-73632
Species: Homo sapiens
Compartment: cytosol
Cytosolic thymidine kinase 1 (TK1) catalyzes the reaction of thymidine and ATP to form TMP (thymidine 5'-monophosphate) and ADP. TK1 has been purified from human spleen and from cultured cells. The enzyme is active as a homotetramer, and phosphorylates thymidine and deoxyuridine using ATP as a phosphate donor in vitro (Sherley and Kelly 1988a; Munch-Petersen et al. 1991; Birringer et al. 2005). Divalent cations are required for enzyme activity (Mg++ is preferred) (Lee and Cheng 1986), and ATP stabilizes the tetrameric form of the enzyme (Munch-Petersen et al. 1993). In cells, enzyme activity is high during S phase of the cell cycle and low otherwise, correlated with intracellular levels of thymidine kinase 1 protein (Sherley and Kelly 1988b), and consistent with a requirement for TMP synthesis in normal cells only as part of DNA replication.
Identifier: R-HSA-8953452
Species: Homo sapiens
Compartment: nucleoplasm
The E2F6.com-1 complex, consisting of transcription factors E2F6, TFDP1 (DP 1), MGA, MAX, histone methyltransferases EHMT1 (GLP) and EHMT2 (G9a), in complex with CBX3 (HP1gamma) and likely PRC1.6, binds to the E2F1 gene promoter. Presence of PRC1.6 components at the E2F1 gene promoter has not been tested, but is assumed based on association of PRC1.6-interacting protein CBX3 with the E2F1 promoter and the joint binding of CBX3 and PRC1.6 to the E2F6.com-1 complex (Ogawa et al. 2002). Besides the E2F1 gene promoter, the complex of E2F6.com-1 with CBX3 and possibly PRC1.6 was shown to bind to promoters of other genes involved in cell cycle progression, namely MYC, CDC25A and TK1 (Ogawa et al. 2002). However, transcriptional regulation of MYC, CDC25A and TK1 by E2F6 has not been directly demonstrated, and therefore association of E2F6 with these gene loci is not shown.

Pathway (2 results from a total of 2)

Identifier: R-HSA-69205
Species: Homo sapiens
Compartment: nucleoplasm
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.

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.

Identifier: R-HSA-8953750
Species: Homo sapiens
E2F6, similar to other E2F proteins, possesses the DNA binding domain, the dimerization domain and the marked box. E2F6, however, does not have a pocket protein binding domain and thus does not interact with the retinoblastoma family members RB1, RBL1 (p107) and RBL2 (p130) (Gaubatz et al. 1998, Trimarchi et al. 1998, Cartwright et al. 1998). E2F6 lacks the transactivation domain and acts as a transcriptional repressor (Gaubatz et al. 1998, Trimarchi et al. 1998, Cartwright et al. 1998). E2F6 forms a heterodimer with TFDP1 (DP-1) (Trimarchi et al. 1998, Ogawa et al. 2002, Cartwright et al. 1998) or TFDP2 (DP-2) (Gaubatz et al. 1998, Trimarchi et al. 1998, Cartwright et al. 1998).

E2f6 knockout mice are viable and embryonic fibroblasts derived from these mice proliferate normally. Although E2f6 knockout mice appear healthy, they are affected by homeotic transformations of the axial skeleton, involving vertebrae and ribs. Similar skeletal defects have been reported in mice harboring mutations in polycomb genes, suggesting that E2F6 may function in recruitment of polycomb repressor complex(es) to target promoters (Storre et al. 2002).

E2F6 mediates repression of E2F responsive genes. While E2F6 was suggested to maintain G0 state in quiescent cells (Gaubatz et al. 1998, Ogawa et al. 2002), this finding has been challenged (Giangrande et al. 2004, Bertoli et al. 2013, Bertoli et al. 2016). Instead, E2F6-mediated gene repression in proliferating (non-quiescent) cells is thought to repress E2F targets involved in G1/S transition during S phase of the cell cycle. E2F6 does not affect E2F targets involved in G2/M transition (Oberley et al. 2003, Giangrande et al. 2004, Attwooll et al. 2005, Trojer et al. 2011, Bertoli et al. 2013). In the context of the E2F6.com-1 complex, E2F6 was shown to bind to promoters of E2F1, MYC, CDC25A and TK1 genes (Ogawa et al. 2002). E2F6 also binds the promoters of CDC6, RRM1 (RR1), PCNA and TYMS (TS) genes (Giangrande et al. 2004), as well as the promoter of the DHFR gene (Gaubatz et al. 1998). While transcriptional repression by the E2F6.com 1 complex may be associated with histone methyltransferase activity (Ogawa et al. 2002), E2F6 can also repress transcription independently of H3K9 methylation (Oberley et al. 2003).

During S phase, E2F6 is involved in the DNA replication stress checkpoint (Bertoli et al. 2013, Bertoli et al. 2016). Under replication stress, CHEK1-mediated phosphorylation prevents association of E2F6 with its target promoters, allowing transcription of E2F target genes whose expression is needed for resolution of stalled replication forks and restart of DNA synthesis. Inability to induce transcription of E2F target genes (due to CHEK1 inhibition or E2F6 overexpression) leads to replication stress induced DNA damage (Bertoli et al. 2013, Bertoli et al. 2016). E2F6 represses transcription of a number of E2F targets involved in DNA synthesis and repair, such as RRM2, RAD51, BRCA1, and RBBP8 (Oberley et al. 2003, Bertoli et al. 2013).

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