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p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase.

Publication ,  Journal Article
Zhao, Y; Chaiswing, L; Velez, JM; Batinic-Haberle, I; Colburn, NH; Oberley, TD; St Clair, DK
Published in: Cancer Res
May 1, 2005

The tumor suppressor gene p53 is activated by reactive oxygen species-generating agents. After activation, p53 migrates to mitochondria and nucleus, a response that eventually leads to apoptosis, but how the two events are related is unknown. Herein, we show that p53 translocation to mitochondria precedes its translocation to nucleus in JB6 skin epidermal cells treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Translocation of p53 to mitochondria occurs within 10 minutes after TPA application. In the mitochondria, p53 interacts with the primary antioxidant enzyme, manganese superoxide dismutase (MnSOD), consistent with the reduction of its superoxide scavenging activity, and a subsequent decrease of mitochondrial membrane potential. In contrast to the immediate action on mitochondria, p53 transcriptional activity in the nucleus increases at 1 hour following TPA application, accompanied by an increase in the levels of its target gene bax at 15 hours following TPA treatment. Activation of p53 transcriptional activity is preventable by application of a SOD mimetic (MnTE-2-PyP5+). Thus, p53 translocation to mitochondria and subsequent inactivation of MnSOD explains the observed mitochondrial dysfunction, which leads to transcription-dependent mechanisms of p53-induced apoptosis.

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

May 1, 2005

Volume

65

Issue

9

Start / End Page

3745 / 3750

Location

United States

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Suppressor Protein p53
  • Transcriptional Activation
  • Tetradecanoylphorbol Acetate
  • Superoxide Dismutase
  • Skin Neoplasms
  • Skin
  • Proto-Oncogene Proteins c-bcl-2
  • Oncology & Carcinogenesis
  • Mitochondria
 

Citation

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Zhao, Y., Chaiswing, L., Velez, J. M., Batinic-Haberle, I., Colburn, N. H., Oberley, T. D., & St Clair, D. K. (2005). p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res, 65(9), 3745–3750. https://doi.org/10.1158/0008-5472.CAN-04-3835
Zhao, Yunfeng, Luksana Chaiswing, Joyce M. Velez, Ines Batinic-Haberle, Nancy H. Colburn, Terry D. Oberley, and Daret K. St Clair. “p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase.Cancer Res 65, no. 9 (May 1, 2005): 3745–50. https://doi.org/10.1158/0008-5472.CAN-04-3835.
Zhao Y, Chaiswing L, Velez JM, Batinic-Haberle I, Colburn NH, Oberley TD, et al. p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res. 2005 May 1;65(9):3745–50.
Zhao, Yunfeng, et al. “p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase.Cancer Res, vol. 65, no. 9, May 2005, pp. 3745–50. Pubmed, doi:10.1158/0008-5472.CAN-04-3835.
Zhao Y, Chaiswing L, Velez JM, Batinic-Haberle I, Colburn NH, Oberley TD, St Clair DK. p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res. 2005 May 1;65(9):3745–3750.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

May 1, 2005

Volume

65

Issue

9

Start / End Page

3745 / 3750

Location

United States

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Suppressor Protein p53
  • Transcriptional Activation
  • Tetradecanoylphorbol Acetate
  • Superoxide Dismutase
  • Skin Neoplasms
  • Skin
  • Proto-Oncogene Proteins c-bcl-2
  • Oncology & Carcinogenesis
  • Mitochondria