1. Cell Biology
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Retinoblastoma Protein: Disruptive influence

  1. Giulio Cossu  Is a corresponding author
  2. Artal Moreno-Fortuny  Is a corresponding author
  3. Urmas Roostalu  Is a corresponding author
  1. University of Manchester, United Kingdom
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Cite this article as: eLife 2013;2:e01779 doi: 10.7554/eLife.01779
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Figures

A simplified scheme showing the translocation of Rb from the nucleus to the cytoplasm, and the effect it has on sarcomeres.

TNF-α (tumour necrosis factor-alpha) is a cytokine that may, in certain cases, kill cancer cells. When TNF-α binds to its receptor on the surface of a normal cell (1), it triggers a signal transduction cascade that leads to the phosphorylation of Rb in the nucleus (2) by the enzyme CDK4. The phosphorylated Rb (3) separates from the DNA, allowing transcription of E2F target genes, and moves to the cytoplasm, where it binds to mDia1 at the Z line (4). This leads to the destabilization of the actin filaments in the sarcomere and to impaired muscle function. The enzyme SMYD methylates the Rb, which contributes to sarcomere stability (5). There is also evidence that Rb accumulates in the mitochondria, where it seems to play a role in apoptosis (6). The figure was produced using Servier Medical Art (http://www.servier.com).

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