External Collection

  • Access to: E2F1 Map
  • A modularized map of E2F1 in tumor progression and metastasis.

    In the last years a number of research groups have deployed methodologies based on the reconstruction of cancer-associated networks and used them to analyze high-throughput cancer data. A top deregulated cancer network is the one controlled by the E2F family of transcription factors. The most prominent member of this family, E2F1, is involved in a number of essential cancer-related cellular processes such as proliferation, apoptosis and differentiation. In the context of solid tumors, unbalanced E2F1 regulation can lead to the emergence of aggressive tumor cells, which drive cancer progression, resistance to anti-cancer drugs and the rise of metastatic lesions. E2F1 is a remarkable example of a network hub, a protein interacting with many genes, proteins, and other transcription factors through a variety of regulatory mechanisms.

    To understand how E2F1 interacts with different molecules and how it mediates cancer related processes, we constructed a functionally modularized comprehensive interaction map based on the manual exploration of over 800 publications about E2F1 and E2F family proteins, as well as connected pathways playing a role in cancer-related cellular processes. In order to improve visualization, we modularized the map into regulatory, functional and phenotypic parts:

    Extra-/Intracellular Receptor Signaling: Cellular receptors and ligands with known crosstalk to E2F family pathways and additionally cancer relevant receptors that feed downstream processes like cell cycle, apoptosis or survival.

    E2F1 modifications: 1) Post-translational Modifiers of E2F1, containing factors that regulate E2F1 protein stability, for example, upon phosphorylation after DNA damage, 2) Regulators of E2F1 Transcriptional Activity, containing protein binding partners that regulate the affinity or specificity of E2F1 to its DNA targets.

    Cell Cycle: Cyclins, CDKs and MYC that regulate the cell cycle upon extracellular stimulation by growth factors. It also harbors the regulation of expression and activity (e.g. inhibition by RB1) of E2F1-4 as central cell cycle regulators.

    Quiescence: This part encloses factors involved in arresting the cell cycle, as well as complexes that silence E2F1 targets during G0/G1/G2-phase or quiescence.

    DNA-repair: DNA damage sensing and repair factors.

    Apoptosis: Factors inducing and executing the cellular apoptotic program.

    Survival: Factors suppressing pro-apoptotic signaling.

    EMT/invasion/angiogenesis: Known players in EMT like ZEB1/2, SNAI1/2, VIM, CDH1/2, the CTNNB1 regulation and its influence on CDH1 as well as angiogenesis and extracellular matrix regulating factors.

    Metabolism: Since there is recent evidence indicating a regulatory role for E2Fs in the cellular metabolome, we included ion channels and metabolic enzymes in this compartment.

    Contibuted by:

    Dr. Shailendra K Gupta
    Dept. of Systems Biology and Bioinformatics
    University of Rostock

    Khan FM., Marquardt S., Gupta SK., Knoll S., Schmitz U., Spitschak A., Engelmann D., Vera J., Wolkenhauer O., PĆ¼tzer BM. Unraveling a tumor type-specific regulatory core underlying E2F1-mediated epithelial-mesenchymal transition to predict receptor protein signatures. Nat Commun. 2017, Aug 4; 8(1):198. PMID:28775339