this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 20 citations 2025-12-26T20:00:24.753491

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and verification. We verified the target: Homo sapiens MYC (UniProt P01106) encodes the Myc proto-oncogene protein, a nuclear bHLH–leucine zipper transcription factor that heterodimerizes with MAX to bind E-box DNA elements and can repress via MIZ1; it contains conserved Myc boxes and is regulated by a T58/S62 phosphodegron recognized by FBXW7 (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11, jha2023mycfunctionand pages 14-14).

Category Summary Key evidence
Core identity & domains Gene: MYC (human). Key domains: N-terminal transactivation region with conserved Myc boxes (MBI–MBIV) and C-terminal basic helix–loop–helix leucine zipper (bHLH-LZ) for dimerization/DNA binding. (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7)
Mechanism (DNA binding & partners) Forms obligate heterodimer with MAX to bind canonical E-box motifs (e.g., CACGTG) and activates transcription; interacts with MIZ1 to repress specific targets; nuclear localization at promoters/enhancers/super-enhancers. (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11)
Post-translational regulation Regulated by phosphorylation at S62/T58 (GSK3β-linked priming) creating a phospho-degron recognized by FBXW7 leading to ubiquitin-mediated proteasomal degradation. (jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15)
2023–2024 advances Phase-separation/condensate behavior modulates MYC/N-MYC-driven transcriptional programs; genome-wide CRISPR/DepMap screens identify nucleocytoplasmic transport as a MYC synthetic-lethal pathway with XPO1 as a druggable node; building translational dependency maps links cell-line dependencies to TCGA patient tumors. (jha2023mycfunctionand pages 14-15, deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8, issa2024genomicdependenciesin pages 127-129)
Applications / clinical implementations Direct inhibitor: Omomyc-derived miniprotein OMO-103 completed Phase 1 (first-in-human) with RP2D DL5 (6.48 mg/kg); indirect approaches include XPO1 inhibitors, BET bromodomain and CDK9 inhibitors and degraders/PROTACs in development. (garralda2024myctargetingby pages 1-2, deutzmann2024nucleartocytoplasmic pages 1-2, weber2023strategiestotarget pages 1-3, yu2025rethinkingmycinhibition pages 4-5)
Quantitative statistics OMO-103 Phase 1: 22 patients enrolled, 19 evaluable, 12 reached 9-week assessment, 8 had stable disease, 1 achieved 49% tumor-volume reduction; estimated MYC overexpression contributes to >50% of cancers and MYC-network alterations in >70% of HCC; MYC regulates on the order of >11% of human genes. (garralda2024myctargetingby pages 1-2, deutzmann2024nucleartocytoplasmic pages 1-2, issa2024genomicdependenciesin pages 31-35)

Table: Compact, evidence-linked summary of human MYC (P01106) covering domains, mechanism, key 2023–2024 advances, clinical applications (OMO-103), and quantitative statistics; citations link to the supporting context IDs.

Comprehensive research report

  1. Key concepts and definitions (current understanding)
  2. Identity and domains: MYC is a human bHLH-LZ transcription factor with an N-terminal transactivation domain harboring conserved Myc boxes (MBI–MBIV) and a C‑terminal bHLH‑LZ that mediates MAX dimerization and sequence-specific DNA binding to E-boxes (canonical CACGTG) at promoters and enhancers/super-enhancers (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7).
  3. Partners and DNA binding: MYC forms obligate heterodimers with MAX to bind E-box motifs; it can also interact with MIZ1 to repress transcription of cell-cycle inhibitors, integrating activation and repression programs in the nucleus (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11).
  4. Cellular localization and function: MYC acts in the nucleus as a transcriptional amplifier influencing cell-cycle progression, ribosome biogenesis, and metabolic programs; it engages basal transcription machinery (e.g., TBP, P-TEFb) and enhancer architecture (super-enhancers) (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11).

  5. Post-translational regulation and turnover: Phosphorylation at Ser62 and Thr58 forms a phospho-degron; GSK3β-dependent phosphorylation primes FBXW7 recognition and ubiquitin–proteasome degradation, tightly controlling MYC stability (jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15).

  6. Recent developments and latest research (prioritizing 2023–2024)

  7. MYC condensates and phase separation: Emerging work shows that phase separation of Myc/N‑Myc can modulate target-selective transcriptional programs, linking intrinsically disordered regions and condensate biology to MYC-driven gene control (jha2023mycfunctionand pages 14-15). While functional consequences are still being refined, these studies support a condensate-based layer of MYC regulation that may intersect with enhancer topology.
  8. Pan-cancer dependencies and translational maps: Recent efforts to translate cell-line essentiality into patient tumors have produced translational dependency maps connecting gene dependencies to TCGA tumors; MYC-associated programs emerge as core vulnerabilities across cancers, providing a framework for clinical prioritization (issa2024genomicdependenciesin pages 127-129).
  9. Synthetic lethality via nucleocytoplasmic transport in MYC-high HCC (2024): A genome-wide CRISPR screen in a MYC-driven hepatocellular carcinoma model identified 1,808 MYC synthetic-lethal (MYC‑SL) genes with a prominent nucleocytoplasmic transport node; inhibiting Exportin‑1 (XPO1) caused marked tumor regression in a MYC-transgenic HCC model and reduced growth in HCC PDXs, with XPO1 high expression correlating with poor prognosis specifically in MYC‑high HCC (Nature Communications, Feb 2024; https://doi.org/10.1038/s41467-024-45128-y) (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).

  10. Regulatory RNAs and PTM crosstalk: Recent syntheses underscore long noncoding RNA effects on MYC expression/activity and SUMO–CDK9 axis crosstalk affecting transcriptional amplification, reflecting multilayered post-transcriptional and PTM control of the MYC network (jha2023mycfunctionand pages 14-15).

  11. Current applications and real-world implementations

  12. Direct MYC inhibitors: Omomyc/OMO‑103. A first-in-human Phase 1 trial (Nature Medicine, Feb 2024; NCT04808362) tested OMO‑103 (91 aa Omomyc-derived miniprotein). Twenty-two patients enrolled; of 19 evaluable, 12 reached the predefined 9-week assessment; eight had stable disease and one achieved a 49% tumor-volume reduction; most adverse events were grade 1 infusion reactions. Pharmacokinetics showed a ~40 h serum half-life; recommended Phase 2 dose: 6.48 mg/kg (DL5). URL: https://doi.org/10.1038/s41591-024-02805-1 (garralda2024myctargetingby pages 1-2).
  13. Indirect strategies and synthetic-lethal targeting: XPO1 inhibition as a MYC‑SL approach in MYC‑high HCC demonstrates in vivo tumor regression and PDX growth inhibition, nominating nucleocytoplasmic transport as a druggable MYC dependency (Nature Communications 2024: https://doi.org/10.1038/s41467-024-45128-y) (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8). Reviews catalog indirect modalities, including BET and CDK9 inhibitors, and emergent degraders/PROTACs directed at MYC or its co-dependencies (Frontiers in Oncology, 2023: https://doi.org/10.3389/fonc.2023.1142111) (weber2023strategiestotarget pages 1-3). Additional overviews summarize PROTAC and epigenomic strategies in early clinical testing (yu2025rethinkingmycinhibition pages 4-5).

  14. Ongoing/announced trials: The Omomyc program continues into disease-focused studies following NCT04808362; multiple early-phase efforts explore indirect MYC suppression (e.g., BET/CDK9) and MYC‑centric degraders as summarized in recent reviews (garralda2024myctargetingby pages 1-2, yu2025rethinkingmycinhibition pages 4-5).

  15. Expert opinions and analysis from authoritative sources

  16. Authoritative trial report: Nature Medicine’s Phase 1 OMO‑103 publication provides clinical-grade evidence of feasibility, tolerability, target engagement, and preliminary antitumor activity for direct MYC inhibition in solid tumors (garralda2024myctargetingby pages 1-2).
  17. Mechanistic consensus syntheses: Contemporary reviews detail MYC’s multi-modal regulation as a nuclear bHLH-LZ factor integrating activation via MAX and repression via MIZ1, with critical control by phospho‑degron/FBXW7 pathways and engagement with enhancer architecture and transcriptional machinery (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11).

  18. Translational dependency and SL analysis: Nature Communications (2024) offers high-quality experimental evidence that MYC‑high tumors depend on nucleocytoplasmic transport, providing a practical therapeutic entry point (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).

  19. Relevant statistics and data (recent)

  20. OMO‑103 (Phase 1): 22 patients enrolled; 19 evaluable; 12 reached 9-week assessment; 8/12 stable disease; 1 patient with 49% volume reduction; RP2D 6.48 mg/kg; serum t1/2 ~40 h; common TRAEs grade 1 infusion reactions (garralda2024myctargetingby pages 1-2).
  21. MYC dysregulation prevalence (HCC and general): The MYC network is altered in >70% of HCC; MYC overexpression contributes to >50% of human cancers overall, underscoring pan-cancer centrality (deutzmann2024nucleartocytoplasmic pages 1-2).
  22. Scope of MYC regulation: MYC/MAX binding regulates on the order of >11% of human genes (genome-wide mapping/E-box occupancy estimates), illustrating its broad transcriptional reach (issa2024genomicdependenciesin pages 31-35).

Mechanistic placement in pathways and subcellular localization
- Primary role: Nuclear transcription factor that directly binds E-box motifs as a MYC:MAX heterodimer to activate genes involved in cell-cycle progression, biomass accumulation (ribosome biogenesis), and metabolism; represses via MIZ1 complexes, balancing proliferative outputs (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11, issa2024genomicdependenciesin pages 31-35).
- Regulation by PTMs: MYC protein stability is determined by sequential Ser62/Thr58 phosphorylation, promoting FBXW7-mediated ubiquitination and proteasomal degradation (jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15). This turnover gate keeps oncogenic thresholds and creates pharmacologic opportunities via E3 ligase axes.

Clinical and translational implications
- Direct MYC inhibition is now clinically feasible (OMO‑103), with early signals of disease stabilization and acceptable safety; defining biomarkers of benefit will be critical in Phase 2 (garralda2024myctargetingby pages 1-2).
- Indirect targeting of MYC dependencies (e.g., XPO1) is supported by in vivo efficacy, particularly in MYC‑high contexts such as HCC, suggesting patient selection by MYC activity may optimize responses (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).

URLs and publication dates (selection)
- OMO‑103 Phase 1 (Nature Medicine), published Feb 6, 2024: https://doi.org/10.1038/s41591-024-02805-1 (garralda2024myctargetingby pages 1-2).
- MYC nucleocytoplasmic transport dependency (Nature Communications), published Feb 2024: https://doi.org/10.1038/s41467-024-45128-y (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).
- Mechanistic review (Frontiers in Cell and Developmental Biology), Oct 2023: https://doi.org/10.3389/fcell.2023.1268275 (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11, jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15).
- Targeting strategies review (Frontiers in Oncology), Mar 2023: https://doi.org/10.3389/fonc.2023.1142111 (weber2023strategiestotarget pages 1-3).

Notes on identification and ambiguity
- The gene symbol MYC here is unambiguous: human Homo sapiens MYC (UniProt P01106), encoding c‑Myc; all cited mechanisms and trials correspond to human MYC biology (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7).

References

  1. (issa2024genomicdependenciesin pages 31-35): LHB Issa. Genomic dependencies in myc overexpressing multiple myeloma. Unknown journal, 2024.

  2. (jha2023mycfunctionand pages 6-7): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 80 citations and is from a poor quality or predatory journal.

  3. (jha2023mycfunctionand pages 11-11): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 80 citations and is from a poor quality or predatory journal.

  4. (jha2023mycfunctionand pages 14-14): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 80 citations and is from a poor quality or predatory journal.

  5. (jha2023mycfunctionand pages 14-15): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 80 citations and is from a poor quality or predatory journal.

  6. (deutzmann2024nucleartocytoplasmic pages 1-2): Anja Deutzmann, Delaney K. Sullivan, Renumathy Dhanasekaran, Wei Li, Xinyu Chen, Ling Tong, Wadie D. Mahauad-Fernandez, John Bell, Adriane Mosley, Angela N. Koehler, Yulin Li, and Dean W. Felsher. Nuclear to cytoplasmic transport is a druggable dependency in myc-driven hepatocellular carcinoma. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45128-y, doi:10.1038/s41467-024-45128-y. This article has 13 citations and is from a highest quality peer-reviewed journal.

  7. (deutzmann2024nucleartocytoplasmic pages 7-8): Anja Deutzmann, Delaney K. Sullivan, Renumathy Dhanasekaran, Wei Li, Xinyu Chen, Ling Tong, Wadie D. Mahauad-Fernandez, John Bell, Adriane Mosley, Angela N. Koehler, Yulin Li, and Dean W. Felsher. Nuclear to cytoplasmic transport is a druggable dependency in myc-driven hepatocellular carcinoma. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45128-y, doi:10.1038/s41467-024-45128-y. This article has 13 citations and is from a highest quality peer-reviewed journal.

  8. (issa2024genomicdependenciesin pages 127-129): LHB Issa. Genomic dependencies in myc overexpressing multiple myeloma. Unknown journal, 2024.

  9. (garralda2024myctargetingby pages 1-2): Elena Garralda, Marie-Eve Beaulieu, Víctor Moreno, Sílvia Casacuberta-Serra, Sandra Martínez-Martín, Laia Foradada, Guzman Alonso, Daniel Massó-Vallés, Sergio López-Estévez, Toni Jauset, Elena Corral de la Fuente, Bernard Doger, Tatiana Hernández, Raquel Perez-Lopez, Oriol Arqués, Virginia Castillo Cano, Josefa Morales, Jonathan R. Whitfield, Manuela Niewel, Laura Soucek, and Emiliano Calvo. Myc targeting by omo-103 in solid tumors: a phase 1 trial. Nature Medicine, 30:762-771, Feb 2024. URL: https://doi.org/10.1038/s41591-024-02805-1, doi:10.1038/s41591-024-02805-1. This article has 149 citations and is from a highest quality peer-reviewed journal.

  10. (weber2023strategiestotarget pages 1-3): Leonie I. Weber and Markus Hartl. Strategies to target the cancer driver myc in tumor cells. Frontiers in Oncology, Mar 2023. URL: https://doi.org/10.3389/fonc.2023.1142111, doi:10.3389/fonc.2023.1142111. This article has 28 citations and is from a poor quality or predatory journal.

  11. (yu2025rethinkingmycinhibition pages 4-5): Jing Yu, Dan Liu, Yujian Yuan, Chunxia Sun, and Zihan Su. Rethinking myc inhibition: a multi-dimensional approach to overcome cancer’s master regulator. Frontiers in Cell and Developmental Biology, Apr 2025. URL: https://doi.org/10.3389/fcell.2025.1601975, doi:10.3389/fcell.2025.1601975. This article has 3 citations and is from a poor quality or predatory journal.

Citations

  1. jha2023mycfunctionand pages 14-15
  2. issa2024genomicdependenciesin pages 127-129
  3. garralda2024myctargetingby pages 1-2
  4. weber2023strategiestotarget pages 1-3
  5. yu2025rethinkingmycinhibition pages 4-5
  6. deutzmann2024nucleartocytoplasmic pages 1-2
  7. issa2024genomicdependenciesin pages 31-35
  8. jha2023mycfunctionand pages 6-7
  9. jha2023mycfunctionand pages 11-11
  10. jha2023mycfunctionand pages 14-14
  11. deutzmann2024nucleartocytoplasmic pages 7-8
  12. https://doi.org/10.1038/s41467-024-45128-y
  13. https://doi.org/10.1038/s41591-024-02805-1
  14. https://doi.org/10.3389/fonc.2023.1142111
  15. https://doi.org/10.3389/fcell.2023.1268275
  16. https://doi.org/10.3389/fcell.2023.1268275,
  17. https://doi.org/10.1038/s41467-024-45128-y,
  18. https://doi.org/10.1038/s41591-024-02805-1,
  19. https://doi.org/10.3389/fonc.2023.1142111,
  20. https://doi.org/10.3389/fcell.2025.1601975,