Transformation suppressor protein Pdcd4 interferes with JNK-mediated phosphorylation of c-Jun and recruitment of the coactivator p300 by c-Jun

Oncogene
N BitomskyK H Klempnauer

Abstract

The transformation suppressor gene Pdcd4 (programmed cell death gene 4) inhibits the tumor-promoter mediated transformation of mouse keratinocytes and has recently been implicated as a potential tumor suppressor gene in the development of human lung cancer. Biochemical analysis has suggested that the Pdcd4 protein is involved in protein translation as well as in nuclear events. Recent work has shown that Pdcd4 suppresses the transactivation of AP-1 responsive promoters by c-Jun, suggesting that the transformation-suppressor activity of Pdcd4 might be due, at least in part, to the inhibition of c-Jun activity. Here, we have addressed how Pdcd4 inhibits c-Jun. We show that Pdcd4 interferes with the phosphorylation of c-Jun by Jun N-terminal kinase (JNK). The inhibition of c-Jun phosphorylation by Pdcd4 appears not to be due to a general suppression of JNK activity, our data rather suggest that Pdcd4 interacts with c-Jun and thereby blocks phosphorylation of c-Jun. In addition to affecting c-Jun phosphorylation, Pdcd4 blocks the recruitment of the coactivator p300 by c-Jun. Taken together, our results strongly suggest that Pdcd4 is directly involved in the regulation of c-Jun activity.

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Citations

Jan 16, 2013·Oncogene·V J Sanchez-Arévalo LoboB Amati
Oct 29, 2011·The Journal of Biological Chemistry·Lena WedekenKarl-Heinz Klempnauer
Aug 13, 2010·Journal of Clinical Pathology·Matteo FassanMassimo Rugge
Mar 29, 2011·Gastroenterology·H Nikki March, Douglas J Winton
Apr 3, 2010·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ying JiangCheng Yong Qin
Dec 10, 2009·Biochemical and Biophysical Research Communications·Chun-Ho KimKyung-Sook Chung
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Sep 17, 2008·Journal of Cellular and Molecular Medicine·Fei GaoLining Zhang
Apr 10, 2009·Biology of the Cell·Brigitte Lankat-Buttgereit, Rüdiger Göke
Jan 30, 2009·Journal of Cellular and Molecular Medicine·Anna M Krichevsky, Galina Gabriely
Apr 18, 2015·Biochimica Et Biophysica Acta·Cinzia FranchinLorenzo A Pinna
Sep 16, 2015·Cell Communication and Signaling : CCS·Bianca KloosKatharina F Kubatzky
May 2, 2012·The International Journal of Biochemistry & Cell Biology·Rui JinGuo-Ping Zhou
May 8, 2010·Journal of Hepatology·Changzheng LiuSongsen Chen
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Jul 6, 2015·Archives of Biochemistry and Biophysics·Gang WangShing Shun Tony To
Sep 23, 2014·Biochimica Et Biophysica Acta·Jennifer Chu, Jerry Pelletier

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