Search results for RUNX1

Showing 21 results out of 282

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Protein (3 results from a total of 5)

Identifier: R-HSA-5667138
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: RUNX1: Q01196
Identifier: R-HSA-8865295
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: RUNX1: Q01196
Identifier: R-HSA-8937712
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: Q01196

Interactor (3 results from a total of 4)

Identifier: Q01196-8
Species: Homo sapiens
Primary external reference: UniProt: Q01196-8
Identifier: Q01196-1
Species: Homo sapiens
Primary external reference: UniProt: Q01196-1
Identifier: Q06455-2
Species: Homo sapiens
Primary external reference: UniProt: Q06455-2

RNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8935779
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: ENST00000344691

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8951912
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000159216

Reaction (3 results from a total of 145)

Identifier: R-HSA-8938853
Species: Homo sapiens
Compartment: nucleoplasm
CDK6 binds to the Runt domain of RUNX1 and interferes with RUNX1 binding to DNA and transcription co-factors. Formation of the RUNX1:CBFB complex does not affect the ability of CDK6 to interact with RUNX1. Neither the catalytic activity nor the cyclin-binding activity of CDK6 are required for its association with RUNX1 (Fujimoto et al. 2007).
Identifier: R-HSA-8865482
Species: Homo sapiens
Compartment: nucleoplasm
Histone methyltransferase KMT2A (MLL) binds to RUNX1 (AML1) both in the presence and absence of CBFB (Huang et al. 2011).
Identifier: R-HSA-8934735
Species: Homo sapiens
Compartment: nucleoplasm
Protein arginine methyltransferase 1 (PRMT1) methylates arginine residues R206 and R210 of RUNX1. Methylation of R206 and R210 inhibits binding of co-repressors to RUNX1, thus enhancing RUNX1 transcriptional activity (Zhao et al. 2008). In mice, arginine methylation seems to be dispensable for the function of RUNX1 in definitive hematopoiesis and steady-state platelet production, but is needed for the maintenance of the peripheral population of CD4+ T cells (Mizutani et al. 2015).

Pathway (3 results from a total of 22)

Identifier: R-HSA-8878171
Species: Homo sapiens
The RUNX1 (AML1) transcription factor is a master regulator of hematopoiesis (Ichikawa et al. 2004) that is frequently translocated in acute myeloid leukemia (AML), resulting in formation of fusion proteins with altered transactivation profiles (Lam and Zhang 2012, Ichikawa et al. 2013). In addition to RUNX1, its heterodimerization partner CBFB is also frequently mutated in AML (Shigesada et al. 2004, Mangan and Speck 2011).
The core domain of CBFB binds to the Runt domain of RUNX1, resulting in formation of the RUNX1:CBFB heterodimer. CBFB does not interact with DNA directly. The Runt domain of RUNX1 mediated both DNA binding and heterodimerization with CBFB (Tahirov et al. 2001), while RUNX1 regions that flank the Runt domain are involved in transactivation (reviewed in Zhang et al. 2003) and negative regulation (autoinhibition). CBFB facilitates RUNX1 binding to DNA by stabilizing Runt domain regions that interact with the major and minor grooves of the DNA (Tahirov et al. 2001, Backstrom et al. 2002, Bartfeld et al. 2002). The transactivation domain of RUNX1 is located C-terminally to the Runt domain and is followed by the negative regulatory domain. Autoinhibiton of RUNX1 is relieved by interaction with CBFB (Kanno et al. 1998).
Transcriptional targets of the RUNX1:CBFB complex involve genes that regulate self-renewal of hematopoietic stem cells (HSCs) (Zhao et al. 2014), as well as commitment and differentiation of many hematopoietic progenitors, including myeloid (Friedman 2009) and megakaryocytic progenitors (Goldfarb 2009), regulatory T lymphocytes (Wong et al. 2011) and B lymphocytes (Boller and Grosschedl 2014).
RUNX1 binds to promoters of many genes involved in ribosomal biogenesis (Ribi) and is thought to stimulate their transcription. RUNX1 loss-of-function decreases ribosome biogenesis and translation in hematopoietic stem and progenitor cells (HSPCs). RUNX1 loss-of-function is therefore associated with a slow growth, but at the same time it results in reduced apoptosis and increases resistance of cells to genotoxic and endoplasmic reticulum stress, conferring an overall selective advantage to RUNX1 deficient HSPCs (Cai et al. 2015).
RUNX1 is implicated as a tumor suppressor in breast cancer. RUNX1 forms a complex with the activated estrogen receptor alpha (ESR1) and regulates expression of estrogen-responsive genes (Chimge and Frenkel 2013).
RUNX1 is overexpressed in epithelial ovarian carcinoma where it may contribute to cell proliferation, migration and invasion (Keita et al. 2013).
RUNX1 may cooperate with TP53 in transcriptional activation of TP53 target genes upon DNA damage (Wu et al. 2013).
RUNX1 is needed for the maintenance of skeletal musculature (Wang et al. 2005).
During mouse embryonic development, Runx1 is expressed in most nociceptive sensory neurons, which are involved in the perception of pain. In adult mice, Runx1 is expressed only in nociceptive sensory neurons that express the Ret receptor and is involved in regulation of expression of genes encoding ion channels (sodium-gated, ATP-gated and hydrogen ion-gated) and receptors (thermal receptors, opioid receptor MOR and the Mrgpr class of G protein coupled receptors). Mice lacking Runx1 show defective perception of thermal and neuropathic pain (Chen CL et al. 2006). Runx1 is thought to activate the neuronal differentiation of nociceptive dorsal root ganglion cells during embryonal development possibly through repression of Hes1 expression (Kobayashi et al. 2012). In chick and mouse embryos, Runx1 expression is restricted to the dorso-medial domain of the dorsal root ganglion, to TrkA-positive cutaneous sensory neurons. Runx3 expression in chick and mouse embryos is restricted to ventro-lateral domain of the dorsal root ganglion, to TrkC-positive proprioceptive neurons (Chen AI et al. 2006, Kramer et al. 2006). RUNX1 mediated regulation of neuronally expressed genes will be annotated when mechanistic details become available.
Identifier: R-HSA-8934593
Species: Homo sapiens
At the level of transcription, expression of the RUNX1 transcription factor is regulated by two alternative promoters: a distal promoter, P1, and a proximal promoter, P2. P1 is more than 7 kb upstream of P2 (Ghozi et al. 1996). In mice, the Runx1 gene is preferentially transcribed from the proximal P2 promoter during generation of hematopoietic cells from hemogenic endothelium. In fully committed hematopoietic progenitors, the Runx1 gene is preferentially transcribed from the distal P1 promoter (Sroczynska et al. 2009, Bee et al. 2010). In human T cells, RUNX1 is preferentially transcribed from P1 throughout development, while developing natural killer cells transcribe RUNX1 predominantly from P2. Developing B cells transcribe low levels of RUNX1 from both promoters (Telfer and Rothenberg 2001).
RUNX1 mRNAs transcribed from alternative promoters differ in their 5'UTRs and splicing isoforms of RUNX1 have also been described. The function of alternative splice isoforms and alternative 5'UTRs has not been fully elucidated (Challen and Goodell 2010, Komeno et al. 2014).
During zebrafish hematopoiesis, RUNX1 expression increases in response to NOTCH signaling, but direct transcriptional regulation of RUNX1 by NOTCH has not been demonstrated (Burns et al. 2005). RUNX1 transcription also increases in response to WNT signaling. BothTCF7 and TCF4 bind the RUNX1 promoter (Wu et al. 2012, Hoverter et al. 2012), and RUNX1 transcription driven by the TCF binding element (TBE) in response to WNT3A treatment is inhibited by the dominant-negative mutant of TCF4 (Medina et al. 2016). In developing mouse ovary, Runx1 expression is positively regulated by Wnt4 signaling (Naillat et al. 2015).
Studies in mouse hematopoietic stem and progenitor cells imply that RUNX1 may be a direct transcriptional target of HOXB4 (Oshima et al. 2011).
Conserved cis-regulatory elements were recently identified in intron 5 of RUNX1. The RUNX1 breakpoints observed in acute myeloid leukemia (AML) with translocation (8;21), which result in expression of a fusion RUNX1-ETO protein, cluster in intron 5, in proximity to these not yet fully characterized cis regulatory elements (Rebolledo-Jaramillo et al. 2014).
At the level of translation, RUNX1 expression is regulated by various microRNAs which bind to the 3'UTR of RUNX1 mRNA and inhibit its translation through endonucleolytic and/or nonendonucleolytic mechanisms. MicroRNAs that target RUNX1 include miR-378 (Browne et al. 2016), miR-302b (Ge et al. 2014), miR-18a (Miao et al. 2015), miR-675 (Zhuang et al. 2014), miR-27a (Ben-Ami et al. 2009), miR-17, miR-20a, miR106 (Fontana et al. 2007) and miR-215 (Li et al. 2016).
At the posttranslational level, RUNX1 activity is regulated by postranslational modifications and binding to co-factors. SRC family kinases phosphorylate RUNX1 on multiple tyrosine residues in the negative regulatory domain, involved in autoinhibition of RUNX1. RUNX1 tyrosine phosphorylation correlates with reduced binding of RUNX1 to GATA1 and increased binding of RUNX1 to the SWI/SNF complex, leading to inhibition of RUNX1-mediated differentiation of T-cells and megakaryocytes. SHP2 (PTPN11) tyrosine phosphatase binds to RUNX1 and dephosphorylates it (Huang et al. 2012).
Formation of the complex with CBFB is necessary for the transcriptional activity of RUNX1 (Wang et al. 1996). Binding of CCND3 and probably other two cyclin D family members, CCND1 and CCND2, to RUNX1 inhibits its association with CBFB (Peterson et al. 2005), while binding to CDK6 interferes with binding of RUNX1 to DNA without affecting formation of the RUNX1:CBFB complex. Binding of RUNX1 to PML plays a role in subnuclear targeting of RUNX1 (Nguyen et al. 2005).
RUNX1 activity and protein levels vary during the cell cycle. RUNX1 protein levels increase from G1 to S and from S to G2 phases, with no increase in RUNX1 mRNA levels. CDK1-mediated phosphorylation of RUNX1 at the G2/M transition is implicated in reduction of RUNX1 transactivation potency and may promote RUNX1 protein degradation by the anaphase promoting complex (reviewed by Friedman 2009).
Identifier: R-HSA-8939243
Species: Homo sapiens
The transcriptional activity of the RUNX1:CBFB complex is regulated by interaction with co-factors and posttranslational modifications of RUNX1. Protein serine/threonine kinase HIPK2 can phosphorylate RUNX1 and affect transcriptional activity of the RUNX1:CBFB complex during hematopoiesis. Some CBFB mutations found in leukemia interfere with HIPK2-mediated phosphorylation of RUNX1. HIPK2 can simultaneously phosphorylate RUNX1 and EP300 (p300) bound to the RUNX1:CBFB1 complex (Aikawa et al. 2006, Wee et al. 2008).
The RUNX1:CBFB complex can associate with the polycomb repressor complex 1 (PRC1). PRC1 complexes are found at many RUNX1 target promoters and can act either as co-activators or co-repressors in the transactivation of RUNX1 targets (Yu et al. 2011).
RUNX1 recruits the SWI/SNF chromatin remodeling complex to many RUNX1 target promoters by directly interacting with several SWI/SNF subunits (Bakshi et al. 2010).
Other co-factors of the RUNX1:CBFB complex are annotated in the context of transcriptional regulation of specific genes.

Complex (3 results from a total of 98)

Identifier: R-HSA-8939132
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8935874
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8935945
Species: Homo sapiens
Compartment: cytosol

Set (3 results from a total of 5)

Identifier: R-HSA-8938850
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8938964
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8935716
Species: Homo sapiens
Compartment: nucleoplasm

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Bruce May
Designer: Cristoffer Sevilla
RUNX1 icon
Runt-related transcription factor 1
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