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Involvement of the DNA Repair Protein hHR23 in p53 Degradation

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2003

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Glockzin, Sandra
Ogi, Francois-Xavier
Hengstermann, Arnd
Blattner, Christine

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Molecular and Cellular Biology. 2003, 23(24), pp. 8960-8969. ISSN 0270-7306. eISSN 1098-5549. Available under: doi: 10.1128/MCB.23.24.8960-8969.2003

Zusammenfassung

The stability of the tumor suppressor protein p53 is regulated via the ubiquitin-proteasome-dependent proteolytic pathway. Like most substrates of this pathway, p53 is modified by the attachment of polyubiquitin chains prior to proteasome-mediated degradation. However, the mechanism(s) involved in the delivery of polyubiquitylated p53 molecules to the proteasome are currently unclear. Here, we show that the human DNA repair protein hHR23 binds to polyubiquitylated p53 via its carboxyl-terminal ubiquitin-associated (Uba) domain shielding p53 from deubiquitylation in vitro and in vivo. In addition, downregulation of hHR23 expression within cells by RNA interference results in accumulation of p53. Since the Ubl domain of hHR23 has been shown to interact with the 26S proteasome, we propose that hHR23 is intrinsically involved in the delivery of polyubiquitylated p53 molecules to the proteasome. In this model, the Uba domain of hHR23 binds to polyubiquitin chains formed on p53 and protects them from deubiquitylation, while the Ubl domain delivers the polyubiquitylated p53 molecules to the proteasome.

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570 Biowissenschaften, Biologie

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ISO 690GLOCKZIN, Sandra, Francois-Xavier OGI, Arnd HENGSTERMANN, Martin SCHEFFNER, Christine BLATTNER, 2003. Involvement of the DNA Repair Protein hHR23 in p53 Degradation. In: Molecular and Cellular Biology. 2003, 23(24), pp. 8960-8969. ISSN 0270-7306. eISSN 1098-5549. Available under: doi: 10.1128/MCB.23.24.8960-8969.2003
BibTex
@article{Glockzin2003-12-15Invol-42657,
  year={2003},
  doi={10.1128/MCB.23.24.8960-8969.2003},
  title={Involvement of the DNA Repair Protein hHR23 in p53 Degradation},
  number={24},
  volume={23},
  issn={0270-7306},
  journal={Molecular and Cellular Biology},
  pages={8960--8969},
  author={Glockzin, Sandra and Ogi, Francois-Xavier and Hengstermann, Arnd and Scheffner, Martin and Blattner, Christine}
}
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