Skp2B attenuates p53 function by inhibiting prohibitin.

EMBO Reports
Harish ChanderDoris Germain

Abstract

The F-box protein Skp2 and its isoform Skp2B are both overexpressed in breast cancers. Skp2 alters the activity of p53 by inhibiting its interaction with p300 and by promoting p300 degradation. Here, we report that Skp2B also attenuates the activity of p53; however, this effect is independent of p300, suggesting that another mechanism might be involved. Prohibitin, a protein reported to activate p53, was isolated in a two-hybrid screen with the carboxy-terminal domain unique to Skp2B. We observed that prohibitin is a new substrate of Skp2B and that the degradation of prohibitin is responsible for the attenuated activity of p53 in cells overexpressing Skp2B. Furthermore, we show that the activity of p53 is reduced in the mammary glands of Skp2B transgenic mice. This study indicates that both Skp2 and Skp2B attenuate p53 activity through different pathways, suggesting that amplification of the Skp2 locus represents a powerful mechanism to attenuate p53 function in cancer.

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Citations

Jan 25, 2011·Cell Division·Doris Germain
Oct 27, 2015·International Journal of Oncology·Pengcheng HeMei Zhang
May 20, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Jian-Kun GaoZhi-Wei Wang
Jan 19, 2013·Journal of Receptor and Signal Transduction Research·Tian-Biao Zhou, Yuan-Han Qin
Mar 26, 2013·Chemistry & Biology·Frédéric ThuaudLaurent Désaubry
Mar 16, 2012·Biochemical and Biophysical Research Communications·Hajime YurugiHiroshi Nakada
May 10, 2016·Biochimica Et Biophysica Acta·Nana ZhengWenyi Wei
Feb 5, 2019·International Journal of Cancer. Journal International Du Cancer·Marcel V Alavi
May 12, 2020·Medicinal Research Reviews·Moges Dessale AsmamawHong-Min Liu
Feb 18, 2020·Cellular and Molecular Life Sciences : CMLS·Dong WangLaurent Désaubry
Apr 20, 2011·Expert Review of Proteomics·Simon Staubach, Franz-Georg Hanisch
Jan 7, 2021·Current Opinion in Oncology·Camila Martin Cardozo, Pierre Hainaut

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