Search results for ETS2

Showing 15 results out of 18

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (3 results from a total of 3)

Identifier: R-HSA-1629811
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: P15036
Identifier: R-HSA-3132735
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: ETS2: P15036

ERF

Identifier: R-HSA-2534321
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: ERF: P50548

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-3209178
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000157557

Reaction (5 results from a total of 8)

Identifier: R-HSA-3132737
Species: Homo sapiens
Compartment: nucleoplasm
Both ETS1 and ETS2 contain a consensus site (PLLTP) for MAPK3 and MAPK1 (ERK1 and ERK2, respectively) in the vicinity of the pointed domain, while the pointed domain contains a docking site needed for ERK1/2 binding to ETS1/2. ETS1 and ETS2 are able to collaborate with RAS in superactivating the promoters that contain RREs (RAS response elements) that include ETS-binding sites. The cooperation of ETS1 and ETS2 with RAS activation is dependent on the phosphorylation of PLLTP threonine residue (T38 in ETS1; T72 in ETS2) (Yang et al. 1996, Seidel et al. 2002). Phosphorylation of ETS1 and ETS2 by ERK1/2 induces a conformational change that increases their affinity for the TAZ domain of the transcriptional coactivator CREBBP (CBP) and the transcriptional activation of RREs (Foulds et al. 2004, Nelson et al. 2010), although ETS1/ETS2 may interact with CREBBP in the absence of phosphorylation (Jayaraman et al. 1999). Phosphorylation of serine residue S41 of ETS1 (corresponds to serine residue S75 of ETS2) may be necessary for full activation of ETS1/2 (Nelson et al. 2010).
Identifier: R-HSA-3209179
Species: Homo sapiens
Compartment: nucleoplasm
Binding of ERF to ETS2 promoter strongly represses ETS2 transcription (Sgouras et al. 1995).
Identifier: R-HSA-3209165
Species: Homo sapiens
Compartment: nucleoplasm
Binding of ID1 to ETS2 inhibits ETS2-mediated activation of p16INK4A transcription (Ohtani et al. 2001).
Identifier: R-HSA-3209177
Species: Homo sapiens
Compartment: nucleoplasm
ERF binds to an ETS-binding site in the ETS2 promoter (Sgouras et al. 1995). Phosphorylation of ERF by activated MAPK1 (ERK2) or MAPK3 (ERK1) interferes with ERF-mediated upregulation of ETS2 (Le Gallic et al. 2004).
Identifier: R-HSA-8979082
Species: Homo sapiens
Compartment: nucleoplasm
ETS2, activated by RAS/RAF/MAP kinase cascade, binds the promoter of p16INK4A in the CDKN2A locus (Ohtani et al. 2001). CDKN2A locus also encodes p14ARF (p19ARF in mouse), but from a different promoter and in a different reading frame. While p16INK4A and p14ARF use different exon 1, (exon 1-alpha and exon 1-beta, respectively), they share exons 2 and 3. However, because the reading frames are different, there is no amino acid sequence similarity between the two proteins (Quelle et al. 1995).

Set (3 results from a total of 3)

Identifier: R-HSA-3132719
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-3132724
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-3200029
Species: Homo sapiens
Compartment: nucleoplasm

Complex (2 results from a total of 2)

Identifier: R-HSA-8979081
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-3209172
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (1 results from a total of 1)

Identifier: R-HSA-2559585
Species: Homo sapiens
Oncogene-induced senescence (OIS) is triggered by high level of RAS/RAF/MAPK signaling that can be caused, for example, by oncogenic mutations in RAS or RAF proteins, or by oncogenic mutations in growth factor receptors, such as EGFR, that act upstream of RAS/RAF/MAPK cascade. Oncogene-induced senescence can also be triggered by high transcriptional activity of E2F1, E2F2 or E2F3 which can be caused, for example, by the loss-of-function of RB1 tumor suppressor.

Oncogenic signals trigger transcription of CDKN2A locus tumor suppressor genes: p16INK4A and p14ARF. p16INK4A and p14ARF share exons 2 and 3, but are expressed from different promoters and use different reading frames (Quelle et al. 1995). Therefore, while their mRNAs are homologous and are both translationally inhibited by miR-24 microRNA (Lal et al. 2008, To et al. 2012), they share no similarity at the amino acid sequence level and perform distinct functions in the cell. p16INK4A acts as the inhibitor of cyclin-dependent kinases CDK4 and CDK6 which phosphorylate and inhibit RB1 protein thereby promoting G1 to S transition and cell cycle progression (Serrano et al. 1993). Increased p16INK4A level leads to hypophosphorylation of RB1, allowing RB1 to inhibit transcription of E2F1, E2F2 and E2F3-target genes that are needed for cell cycle progression, which results in cell cycle arrest in G1 phase. p14-ARF binds and destabilizes MDM2 ubiquitin ligase (Zhang et al. 1998), responsible for ubiquitination and degradation of TP53 (p53) tumor suppressor protein (Wu et al. 1993, Fuchs et al. 1998, Fang et al. 2000). Therefore, increased p14-ARF level leads to increased level of TP53 and increased expression of TP53 target genes, such as p21, which triggers p53-mediated cell cycle arrest and, depending on other factors, may also lead to p53-mediated apoptosis. CDKN2B locus, which encodes an inhibitor of CDK4 and CDK6, p15INK4B, is located in the vicinity of CDKN2A locus, at the chromosome band 9p21. p15INK4B, together with p16INK4A, contributes to senescence of human T-lymphocytes (Erickson et al. 1998) and mouse fibroblasts (Malumbres et al. 2000). SMAD3, activated by TGF-beta-1 signaling, controls senescence in the mouse multistage carcinogenesis model through regulation of MYC and p15INK4B gene expression (Vijayachandra et al. 2003). TGF-beta-induced p15INK4B expression is also important for the senescence of hepatocellular carcinoma cell lines (Senturk et al. 2010).

MAP kinases MAPK1 (ERK2) and MAPK3 (ERK1), which are activated by RAS signaling, phosphorylate ETS1 and ETS2 transcription factors in the nucleus (Yang et al. 1996, Seidel et al. 2002, Foulds et al. 2004, Nelson et al. 2010). Phosphorylated ETS1 and ETS2 are able to bind RAS response elements (RREs) in the CDKN2A locus and stimulate p16INK4A transcription (Ohtani et al. 2004). At the same time, activated ERKs (MAPK1 i.e. ERK2 and MAPK3 i.e. ERK1) phosphorylate ERF, the repressor of ETS2 transcription, which leads to translocation of ERF to the cytosol and increased transcription of ETS2 (Sgouras et al. 1995, Le Gallic et al. 2004). ETS2 can be sequestered and inhibited by binding to ID1, resulting in inhibition of p16INK4A transcription (Ohtani et al. 2004).

Transcription of p14ARF is stimulated by binding of E2F transcription factors (E2F1, E2F2 or E2F3) in complex with SP1 to p14ARF promoter (Parisi et al. 2002).

Oncogenic RAS signaling affects mitochondrial metabolism through an unknown mechanism, leading to increased generation of reactive oxygen species (ROS), which triggers oxidative stress induced senescence pathway. In addition, increased rate of cell division that is one of the consequences of oncogenic signaling, leads to telomere shortening which acts as another senescence trigger.
While OIS has been studied to considerable detail in cultured cells, establishment of in vivo role of OIS has been difficult due to lack of specific biomarkers and its interconnectedness with other senescence pathways (Baek and Ryeom 2017, reviewed in Sharpless and Sherr 2015).

Cite Us!