Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1

Deresa Lee; Sang Joon Park; Ki Sa Sung; Jikyoung Park; Sean Bong Lee; Sang Yoon Park; Hyo Jeong Lee; Jang Won Ahn; So Jung Choi; Seok Geun Lee; Sung Hoon Kim; Duk Hwan Kim; Jhingook Kim; Yongsok Kim; Cheol Yong Choi

doi:10.1038/embor.2011.235

Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1

Deresa Lee, Sang Joon Park, Ki Sa Sung, Jikyoung Park, Sean Bong Lee, Sang Yoon Park, Hyo Jeong Lee, Jang Won Ahn, So Jung Choi, Seok Geun Lee, Sung Hoon Kim, Duk Hwan Kim, Jhingook Kim, Yongsok Kim, Cheol Yong Choi

Department of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	163-169
Number of pages	7
Journal	EMBO Reports
Volume	13
Issue number	2
DOIs	https://doi.org/10.1038/embor.2011.235
State	Published - Jan 2012

Keywords

Novel Ras effector 1
RASSF5
homeodomaininteracting protein kinase 1
oncogene
tumorigenesis

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10.1038/embor.2011.235

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title = "Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1",

abstract = "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.",

keywords = "Novel Ras effector 1, RASSF5, homeodomaininteracting protein kinase 1, oncogene, tumorigenesis",

author = "Deresa Lee and Park, {Sang Joon} and Sung, {Ki Sa} and Jikyoung Park and Lee, {Sean Bong} and Park, {Sang Yoon} and Lee, {Hyo Jeong} and Ahn, {Jang Won} and Choi, {So Jung} and Lee, {Seok Geun} and Kim, {Sung Hoon} and Kim, {Duk Hwan} and Jhingook Kim and Yongsok Kim and Choi, {Cheol Yong}",

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AU - Park, Jikyoung

AU - Lee, Sean Bong

AU - Park, Sang Yoon

AU - Lee, Hyo Jeong

AU - Ahn, Jang Won

AU - Choi, So Jung

AU - Lee, Seok Geun

AU - Kim, Sung Hoon

AU - Kim, Duk Hwan

AU - Kim, Jhingook

AU - Kim, Yongsok

AU - Choi, Cheol Yong

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AB - 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.

KW - Novel Ras effector 1

KW - RASSF5

KW - homeodomaininteracting protein kinase 1

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Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1

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Keywords

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