SurveyE2F1 transcription factor and its impact on growth factor and cytokine signaling

- Growth factors utilize E2F1 transcription factor in promoting entry into cell cycle.
- VEGF-induced activation of E2F1, depending on the cellular oxygen demands, positively or negatively regulates angiogenesis.
- E2F1 induces expression of growth factor receptors VEGFR-1, VEGFR-2, FGF-R and IGF-1R.
- Growth suppressive cytokines can either inhibit or activate E2F1 to suppress cell growth.
- Interferon-mediated growth inhibition involves suppression of E2F1 transcription factor.
- E2F1 mediated growth promotion may overcome interleukin-dependency of some hematopoietic cell lines.

E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ).

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