Molecule Information

General Information of the Molecule (ID: Mol04050)

• Name: MYC proto-oncogene (MYC) ,Homo sapiens
• Synonyms: Class E basic helix-loop-helix protein 39; Proto-oncogene c-Myc; Transcription factor p64
• Molecule Type: Protein
• Gene Name: MYC
• Gene ID: 4609
• Location: chr8:127735434-127742951[+]
• Sequence:
  MDFFRVVENQQPPATMPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAP
  SEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTEL
  LGGDMVNQSFICDPDDETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPA
  RGHSVCSTSSLYLQDLSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSAFSPSSDSLLS
  STESSPQGSPEPLVLHEETPPTTSSDSEEEQEDEEEIDVVSVEKRQAPGKRSESGSPSAG
  GHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVLRQISNNRKCTSP
  RSSDTEENVKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILS
  VQAEEQKLISEEDLLRKRREQLKHKLEQLRNSCA
• 3D-structure: PDB ID: 6.00E+16; Classification: Dna binding protein; Method: X-ray diffraction; Resolution: 2.40 Å
• Function: 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). .
• Uniprot ID: MYC_HUMAN
• Ensembl ID: ENSG00000136997
• HGNC ID: HGNC:7553

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Crizotinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Crizotinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Non-small cell lung carcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.24E-04; Fold-change: 3.89E-01; Z-score: 3.78E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: RPPA
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Using complementary approaches in multiple models, including a MYC-amplified patient-derived cell line and xenograft (LUAD-0006), we established that MYC overexpression induces broad ROS1-TKI resistance. Pharmacologic inhibition of ROS1 combined with MYC knockdown were essential to completely suppress LUAD-0006 cell proliferation compared with either treatment alone. We interrogated cellular signaling in ROS1-TKI-resistant LUAD-0006 and discovered significant differential regulation of targets associated with cell cycle, apoptosis, and mitochondrial function.

References

• Ref 1: MYC Promotes Tyrosine Kinase Inhibitor Resistance in ROS1-Fusion-Positive Lung Cancer. Mol Cancer Res. 2022 May 4;20(5):722-734.
• Ref 2: The Novel Anti-Cancer Agent, SpiD3, Is Cytotoxic in CLL Cells Resistant to Ibrutinib or Venetoclax. Hemato. 2024 Sep;5(3):321-339.