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Role of the Histone Acetyl Transferase Tip60 in the p53 Pathway

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2004

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Legube, Gaëlle
Linares, Laetitia K.
Tyteca, Sandrine
Caron, Cécile
Chevillard-Briet, Martine
Trouche, Didier

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The Journal of Biological Chemistry : JBC. 2004, 279(43), pp. 44825-44833. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M407478200

Zusammenfassung

The histone acetyl transferase Tip60 (HTATIP) shares many properties with the tumor suppressor p53 (TP53). Both proteins are involved in the cellular response to DNA damage, are subjected to proteasomal digestion following Mdm2-mediated ubiquitination, and accumulate after UV irradiation. We found here that knock-down of Tip60 affects the p53-dependent response following actinomycin D treatment, most likely because it inhibits p21 (CDKN1A) accumulation. Moreover, Tip60 is required for p53 to activate the endogenous p21 promoter, suggesting that it functions as a p53 co-activator. However, we also found that knock-down of Tip60 increases the turnover rate of p53 under normal growth conditions. Tip60 interferes with Mdm2-mediated degradation of p53, probably because it affects its subcellular localization. Taken together, our results suggest that Tip60 plays a double role in the p53 pathway: under normal growth conditions, Tip60 contributes to maintain a basal pool of p53 by interfering with its degradation; following DNA damage, Tip60 functions as p53 co-activator. That these two distinct roles are linked during the p53-dependent response is an attractive hypothesis.

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570 Biowissenschaften, Biologie

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ISO 690LEGUBE, Gaëlle, Laetitia K. LINARES, Sandrine TYTECA, Cécile CARON, Martin SCHEFFNER, Martine CHEVILLARD-BRIET, Didier TROUCHE, 2004. Role of the Histone Acetyl Transferase Tip60 in the p53 Pathway. In: The Journal of Biological Chemistry : JBC. 2004, 279(43), pp. 44825-44833. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M407478200
BibTex
@article{Legube2004-10-22Histo-42644,
  year={2004},
  doi={10.1074/jbc.M407478200},
  title={Role of the Histone Acetyl Transferase Tip60 in the p53 Pathway},
  number={43},
  volume={279},
  issn={0021-9258},
  journal={The Journal of Biological Chemistry : JBC},
  pages={44825--44833},
  author={Legube, Gaëlle and Linares, Laetitia K. and Tyteca, Sandrine and Caron, Cécile and Scheffner, Martin and Chevillard-Briet, Martine and Trouche, Didier}
}
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