Skip NavigationSkip to Content
Return Return to Search Results

The death domain kinase RIP has an essential role in DNA damage-induced NF-kappa B activation

  1. Author:
    Hur, G. M.
    Lewis, J.
    Yang, Q. F.
    Lin, Y.
    Nakano, H.
    Nedospasov, S.
    Liu, Z. G.

  2. Author Address

    NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA Japan Sci & Technol Corp, Juntendo Univ, Sch Med, Dept Immunol,PREST, Tokyo, Japan NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA Liu ZG NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
    1. Year: 2003
  2. Journal: Genes & Development
    1. 17
    2. 7
    3. Pages: 873-882
  4. Type of Article: Article
  1. Abstract:

    The transcription factor NF-kappaB is activated when cells are exposed to genotoxic stress. It has been suggested that DNA damage will trigger a cytoplasmic signaling that leads to the activation of IKK and NF-kappaB, but the signaling components upstream of IKK have not yet been identified. Here we report that the receptor interacting protein, RIP, is the IKK upstream component, essential for the activation of NF-kappaB by DNA damage. Also, our findings suggest that this NF-kappaB activation by DNA damage is not mediated by autocrine or TNF-R1 signaling pathway. In wild-type fibroblasts, DNA damage induced by agents such as adriamycin, campthothecin, and ionizing radiation induces NF-kappaB activation. We found, however, that DNA damage failed to activate NF-kappaB in RIP-/- fibroblasts. The induction Of IkappaBalpha degradation by DNA damage was normal in TNF-R1-/-, TRAF2-/-, TRAF5-/- and FADD-/- fibroblasts or when de novo protein synthesis was blocked. More importantly, the reconstitution of RIP expression in RIP-/- cells restores DNA damage-induced NF-kappaB activation. We also found that RIP forms a complex with IKK in response to DNA damage. Therefore, our study provides a possible mechanism for the initiation of the cytoplasmic signaling to activate NF- kappaB in response to DNA damage.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel