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Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1
Author(s) -
Lee Deresa,
Park SangJoon,
Sung Ki Sa,
Park Jikyoung,
Lee Sean Bong,
Park SangYoon,
Lee Hyo Jeong,
Ahn JangWon,
Choi So Jung,
Lee SeokGeun,
Kim SungHoon,
Kim DukHwan,
Kim Jhingook,
Kim Yongsok,
Choi Cheol Yong
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.235
Subject(s) - ubiquitin ligase , mdm2 , effector , ubiquitin , gene silencing , carcinogenesis , biology , microbiology and biotechnology , cell growth , cancer research , epigenetics , embryonic stem cell , cell , cell culture , cancer , biochemistry , genetics , gene
The Ras effector NORE1 is frequently silenced in primary adenocarcinomas, although the significance of this silencing for tumorigenesis is unclear. Here we show that NORE1 induces polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by facilitating its interaction with the Mdm2 E3 ubiquitin ligase. Endogenous HIPK1 is stabilized in Nore1 ‐deficient mouse embryonic fibroblasts, and depletion of HIPK1 in NORE1 ‐silenced lung adenocarcinoma cells inhibits anchorage‐independent cell growth and tumour formation in nude mice. These findings indicate that the control of HIPK1 stability by Mdm2–NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization.