Macrophage Differentiation Pathway

Preferred Label : Macrophage Differentiation Pathway;

NCIt related terms : METS affect on Macrophage Differentiation;

Alternative definition : BIOCARTA: Terminal differentiation of cells is often accompanied by repression of cellular proliferation, suggesting that there is a mechanism by which these cellular functions are coordinated. Macrophage differentiation is one model system in which this occurs; as macrophages differentiate, they also stop proliferating. Transcriptional regulation plays a key role in cell cycle progression as well as many differentiation processes. Ras stimulates cell cycle progression in part through Ets transcription factors that bind to cell cycle regulatory genes to activate their expression. Ets transcription factors also help to induce early macrophage differentiation. The activation of Ras signaling by M-CSF activates transcription of genes involved in differentiation through the coordinate expression of both Ets factors and AP-1. Other genes involved in cell cycle regulation coordinate action of E2F-1 and Ets transcription factors. Mets is a factor related in sequence to Ets2 that is upregulated during macrophage differentiation. Increased expression of the Mets protein during macrophage differentiation allows the creation of heterodimers with DP103 to act as transcriptional repressors of cell cycle progression genes, recruiting corepressor to promoters they interact with. DP103 is a gene previously identified as an RNA helicase involved in RNA processing that interacts with EBNA factors from Epstein Barr Virus. The transcriptional repression involving Mets with DP103 is selective, and does not involve all Ets regulated genes. While cell cycle genes are repressed by Mets, other genes activated by Ets factors such as those involved in differentiation are not repressed by Mets. The transcriptional repression by Mets also involved members of the Rb family of tumor suppressors, such as p107 and p130. This requirement for additional factors involved in regulating proliferation may allow for another level of control on cell proliferation and coordination with differentiation. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_etsPathway;

Details

Origin ID

C39075;

UMLS CUI

C1518151;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- ETS Translocation Variant 3 [NCIt concept]
- GTPase HRas [NCIt concept]
- Histone Deacetylase 2 [NCIt concept]
- Histone Deacetylase 5 [NCIt concept]
- Lysine-Specific Demethylase 6B [NCIt concept]
- Macrophage Colony-Stimulating Factor 1 [NCIt concept]
- Macrophage Colony-Stimulating Factor 1 Receptor [NCIt concept]
- Nuclear Receptor Corepressor 2 [NCIt concept]
- Probable ATP-Dependent RNA Helicase DDX20 [NCIt concept]
- Protein C-ets-1 [NCIt concept]
- Protein C-ets-2 [NCIt concept]
- Proto-Oncogene c-Fos [NCIt concept]
- Retinoblastoma-Like Protein 1 [NCIt concept]
- Retinoblastoma-Like Protein 2 [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- Transcription Factor E2F1 [NCIt concept]
- Transcription Factor E2F4 [NCIt concept]
pathway_has_gene_element
- CSF1 wt Allele [NCIt concept]
- CSF1R wt Allele [NCIt concept]
- DDX20 wt Allele [NCIt concept]
- E2F1 wt Allele [NCIt concept]
- E2F4 wt Allele [NCIt concept]
- ETS1 wt Allele [NCIt concept]
- ETS2 wt Allele [NCIt concept]
- ETV3 wt Allele [NCIt concept]
- FOS wt Allele [NCIt concept]
- HDAC2 wt Allele [NCIt concept]
- HDAC5 wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- KDM6B wt Allele [NCIt concept]
- NCOR2 wt Allele [NCIt concept]
- RBL1 wt Allele [NCIt concept]
- RBL2 wt Allele [NCIt concept]

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