MYC
MYC is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients.
Function
Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000).
Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity).
Biological Process
Beta-catenin-TCF complex assembly Source: Reactome
Branching involved in ureteric bud morphogenesis Source: UniProtKB
Cell cycle arrest Source: UniProtKB
Cellular iron ion homeostasis Source: UniProtKB
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to drug Source: UniProtKB
Cellular response to hypoxia Source: CAFA
Cellular response to UV Source: UniProtKB
Chromatin remodeling Source: UniProtKB
Chromosome organization Source: UniProtKB
Cytokine-mediated signaling pathway Source: Reactome
Energy reserve metabolic process Source: UniProtKB
ERK1 and ERK2 cascade Source: CAFA
Fibroblast apoptotic process Source: UniProtKB
G1/S transition of mitotic cell cycle Source: Reactome
MAPK cascade Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cell division Source: UniProtKB
Negative regulation of fibroblast proliferation Source: UniProtKB
Negative regulation of monocyte differentiation Source: UniProtKB
Negative regulation of stress-activated MAPK cascade Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Notch signaling pathway Source: Reactome
Oxygen transport Source: UniProtKB
Positive regulation of cell population proliferation Source: CAFA
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Positive regulation of DNA biosynthetic process Source: UniProtKB
Positive regulation of DNA methylation Source: BHF-UCL
Positive regulation of epithelial cell proliferation Source: UniProtKB
Positive regulation of fibroblast proliferation Source: UniProtKB
Positive regulation of gene expression Source: CAFA
Positive regulation of mesenchymal cell proliferation Source: UniProtKB
Positive regulation of metanephric cap mesenchymal cell proliferation Source: UniProtKB
Positive regulation of response to DNA damage stimulus Source: UniProtKB
Positive regulation of telomerase activity Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Protein deubiquitination Source: Reactome
Protein-DNA complex disassembly Source: CAFA
Regulation of gene expression Source: MGI
Regulation of somatic stem cell population maintenance Source: UniProtKB
Regulation of telomere maintenance Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to drug Source: UniProtKB
Response to gamma radiation Source: UniProtKB
Response to growth factor Source: UniProtKB
Cellular Location
Nucleoplasm; Nucleolus
Involvement in disease
A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1.
Burkitt lymphoma (BL):
The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass.
PTM
Phosphorylated by PRKDC. Phosphorylation at Ser-329 by PIM2 leads to the stabilization of MYC (By similarity). Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence. Phosphorylated at Ser-62 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-58 and Ser-62 by GSK3 is required for ubiquitination and degradation by the proteasome.
Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-58 and Ser-62, leading to its degradation by the proteasome. In the nucleoplasm, ubiquitination is counteracted by USP28, which interacts with isoform 1 of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation. In the nucleolus, however, ubiquitination is not counteracted by USP28 but by USP36, due to the lack of interaction between isoform 3 of FBXW7 (FBW7gamma) and USP28, explaining the selective MYC degradation in the nucleolus (PubMed:25775507,PubMed:17558397). Also polyubiquitinated by the DCX(TRUSS) complex. Ubiquitinated by TRIM6 in a phosphorylation-independent manner (By similarity).
Loading...
Datasheet