Drug Target and Biomarker: MYC (G4609)

NCBI ID: G4609

Content of Review Report on MYC Target / Biomarker

MYC

Drug Target and Biomarker: MYC

MYC plays a crucial role in both the activation and repression of target genes. It functions as a transcription factor by forming a heterodimer with MAX and binding to specific DNA sequences called E-boxes . This interaction leads to the recruitment of chromatin-modifying complexes and the activation of transcription.

In transcriptional activation, MYC-MAX heterodimers recruit chromatin-modifying co-factors such as TIP60, GCN5, TRRAP, and p300/CBP . These co-factors increase the acetylation of histones, resulting in an open chromatin conformation that allows RNA polymerase II to bind and initiate transcription.

MYC can also repress the transcription of non-canonical target genes by forming complexes with MAX and MIZ1 . This interaction recruits chromatin co-repressors such as DNMT3A, HDAC1, HDAC3, and EZH2, leading to gene silencing .

The stability and activity of MYC are regulated by various factors. Phosphorylation by PIM1 and AURKA increases its stability.

Additionally, WDR5 is crucial for the recruitment of MYC at chromatin regions. There are also specific domains within MYC, known as Myc boxes, that are involved in its functions.

MYC-dependent malignancies can be targeted through various approaches. Pathway inhibitors, BET bromodomain inhibitors, and complex inhibitors have been developed to disrupt MYC signaling and target its transcriptional output. These inhibitors aim to halt the initiation of MYC transcription and interfere with its interactions with co-factors or DNA binding sites.

In summary, MYC is a key transcription factor involved in both the activation and repression of target genes. It forms heterodimers with MAX and interacts with chromatin-modifying co-factors to regulate gene expression. MYC can be targeted for therapeutic purposes in MYC-driven malignancies using specific inhibitors.

The MYC protein, encoded by the MYC gene on chromosome 8, consists of various structural regions and highly conserved MYC boxes at the N-terminal.

MYC is involved in gene transcription, and its accumulation at the promoter sequences of target genes enhances their transcriptional activity.

In hyperglycemic conditions, cancer cells exhibit upregulation of glycolysis mediated by c-Myc, which makes them less sensitive to the energetic stress induced by metformin.

In normoglycemic conditions, metformin inhibits c-Myc expression, preventing the survival-promoting metabolic mechanism associated with increased glycolysis.

Certain deubiquitinating enzymes, such as USP36, USP28, USP22, and USP37, are known to stabilize MYC through deubiquitination processes.

The deregulation of MYC intensifies the expression of both target genes and aberrant nontarget genes, contributing to tumorigenesis.

Physiological Myc is tightly controlled by both transcriptional and post-transcriptional components, while deregulated Myc leads to the upregulation of target genes, including low-affinity ones, and additional nontarget genes, promoting further tumorigenesis.

Knockout of IGF2BPs, in conjunction with depletion of MYC, inhibits cell proliferation, and colony formation in HepG2 cells.

IGF2BPs play a role in the regulation of m6A modified mRNAs, protecting target mRNAs from degradation in the P-body and facilitating translation in the cytoplasm.

Protein Name: MYC Proto-oncogene, BHLH Transcription Factor

Functions: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of growth-related genes (PubMed:24940000, PubMed:25956029). Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000, PubMed:25956029). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells (By similarity). Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808)

The "MYC Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about MYC comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
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