Regulation of XIAP Translation and Induction by MDM2 following Irradiation

Lubing Gu, Ningxi Zhu, Hongying Zhang, Donald L. Durden, Yue Feng, Muxiang Zhou

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Increases in protein levels of XIAP in cancer cells have been associated with resistance to apoptosis induced by cellular stress. Herein we demonstrate that the upregulation of XIAP protein levels is regulated by MDM2 at the translational level. MDM2 was found to physically interact with the IRES of the XIAP 5′-UTR, and to positively regulate XIAP IRES activity. This XIAP IRES-dependent translation was significantly increased in MDM2-transfected cells where MDM2 accumulated in the cytoplasm. Cellular stress and DNA damage triggered by irradiation induced the dephosphorylation and cytoplasmic localization of MDM2, which also led to an increase in IRES-dependent XIAP translation. Upregulation of XIAP in MDM2-overexpressing cancer cells in response to irradiation resulted in resistance of these cells to radiation-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)363-375
Number of pages13
JournalCancer Cell
Volume15
Issue number5
DOIs
StatePublished - May 5 2009

Fingerprint

X-Linked Inhibitor of Apoptosis Protein
Up-Regulation
Apoptosis
5' Untranslated Regions
DNA Damage
Neoplasms
Cytoplasm
Radiation

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Gu, L., Zhu, N., Zhang, H., Durden, D. L., Feng, Y., & Zhou, M. (2009). Regulation of XIAP Translation and Induction by MDM2 following Irradiation. Cancer Cell, 15(5), 363-375. https://doi.org/10.1016/j.ccr.2009.03.002

Regulation of XIAP Translation and Induction by MDM2 following Irradiation. / Gu, Lubing; Zhu, Ningxi; Zhang, Hongying; Durden, Donald L.; Feng, Yue; Zhou, Muxiang.

In: Cancer Cell, Vol. 15, No. 5, 05.05.2009, p. 363-375.

Research output: Contribution to journalArticle

Gu, L, Zhu, N, Zhang, H, Durden, DL, Feng, Y & Zhou, M 2009, 'Regulation of XIAP Translation and Induction by MDM2 following Irradiation', Cancer Cell, vol. 15, no. 5, pp. 363-375. https://doi.org/10.1016/j.ccr.2009.03.002
Gu, Lubing ; Zhu, Ningxi ; Zhang, Hongying ; Durden, Donald L. ; Feng, Yue ; Zhou, Muxiang. / Regulation of XIAP Translation and Induction by MDM2 following Irradiation. In: Cancer Cell. 2009 ; Vol. 15, No. 5. pp. 363-375.
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