Search results for L3MBTL2

Showing 13 results out of 13

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Protein (2 results from a total of 2)

Identifier: R-HSA-6804477
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: L3MBTL2: Q969R5
Identifier: R-HSA-6804480
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: L3MBTL2: Q969R5

Reaction (7 results from a total of 7)

Identifier: R-HSA-6804485
Species: Homo sapiens
Compartment: nucleoplasm
PIAS1 and possibly other SUMO E3 ligases SUMOylates L3MBTL2 with SUMO2 at lysine-675 and lysine-700 near the C-terminus (Stielow et al. 2014, Tammsalu et al. 2014). SUMOylation of L3MBTL2 does not appear to affect its chromatin binding activity, however SUMOylation does enhance transcriptional repression of a subset of L3MBTL2-target genes, particularly those with low L3MBTL2 occupancy including pro-inflammatory genes (Stielow et al. 2014). SUMOylated L3MBTL2 appears to increase the level of local ubiquitinated histone H2A (Stielow et al. 2014).
Identifier: R-HSA-9007462
Species: Homo sapiens
Compartment: nucleoplasm
Binding of the PRC1L4 complex, composed of E2F6, CBX3 (HP1gamma), PCGF6 (MBLR), L3MBTL2 and RING1 or RNF2, to the CDC7 gene promoter represses CDC7 transcription. This is concluded based on experimental evidence of direct association of the PRC1L4 complex with the CDC7 gene promoter and increased CDC7 expression upon E2F6 or L3MBTL2 knockdown (Trojer et al. 2011).
Identifier: R-HSA-9007467
Species: Homo sapiens
Compartment: nucleoplasm
The PRC1L4 complex, consisting of E2F6, CBX3 (HP1gamma), PCGF6 (MBLR), L3MBTL2, and RING1 (RING1A) or RNF2 (RING2, also known as RING1B), binds the promoter of the CDC7 gene (Trojer et al. 2011).
Identifier: R-HSA-9007447
Species: Homo sapiens
Compartment: nucleoplasm
E2F6 forms a complex with CBX3 (HP1gamma) and components of the polycomb repressor complex PRC1.6: PCGF6 (MBLR), L3MBTL2, RING1 (RING1A) or RNF2 (RING2, also known as RING2B). This polycomb repressor-like complex is named PRC1L4. Unlike the complex composed of E2F6.com-1, PRC1.6 and CBX3 (Ogawa et al. 2002), the PRC1L4 complex does not possess histone methyltransferase activity. Instead, the PRC1L4 complex may have a histone E3-ubiquitin ligase activity. The PRC1L4 complex was shown to bind to promoters of several genes: CDC7, CSTF3, MCM3, UXT, RPA2, RAD51C, RFC3, HOXC5. Of these genes, transcriptional repression was tested and demonstrated for CDC7 and UXT (Trojer et al. 2011).
Identifier: R-HSA-9007465
Species: Homo sapiens
Compartment: nucleoplasm
Binding of the PRC1L4 complex, composed of E2F6, CBX3 (HP1gamma), PCGF6 (MBLR), L3MBTL2 and RING1 or RNF2, to the UXT gene promoter represses UXT transcription. This is concluded based on experimental evidence of direct association of the PRC1L4 complex with the UXT gene promoter and increased UXT expression upon E2F6 or L3MBTL2 knockdown (Trojer et al. 2011). E2F6 was also reported as a repressor of the UXT gene transcription by Oberley et al. 2013.
Identifier: R-HSA-9007464
Species: Homo sapiens
Compartment: nucleoplasm
The PRC1L4 complex, consisting of E2F6, CBX3 (HP1gamma), PCGF6 (MBLR), L3MBTL2, and RING1 (RING1A) or RNF2 (RING2, also known as RING1B), binds the promoter of the UXT gene (Trojer et al. 2011). E2F6 was also reported to bind to the UXT promoter by Oberley et al. 2003.
Identifier: R-HSA-9007283
Species: Homo sapiens
Compartment: nucleoplasm
CBX3 (HP1gamma) and the polycomb group (PcG) repressor complex PRC1.6 associate with the E2F6.com-1 complex. The PRC1.6 complex shown to associate with E2F6 consists of PCGF6 (MBLR), RING1 (RING1A) or RNF2 (RING2, also known as RING1B), YAF2 and L3MBTL2. The E2F6.com-1 complex is composed of E2F6, TFDP1 (DP-1), MGA, MAX, EHMT1 (GLP) and EHMT2 (G9a). This complex likely has a histone H3 methyltransferase activity and may be involved in creating the repressive H3K9Me mark at target genes, which would result in transcriptional repression (Ogawa et al. 2002).

Complex (3 results from a total of 3)

Identifier: R-HSA-9007266
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9007476
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9007466
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (1 results from a total of 1)

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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