Journal
EMBO REPORTS
Volume 13, Issue 2, Pages 163-169Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2011.235
Keywords
Novel Ras effector 1; RASSF5; homeodomain-interacting protein kinase 1; oncogene; tumorigenesis
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Funding
- Korea Science and Engineering Foundation (KOSEF) [KRF-2008-313-C00605]
- National Research Foundation [2009-0085548]
- Ministry of Education, Science and Technology [2009-0063466]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK056002] Funding Source: NIH RePORTER
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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.
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