The tumor suppressor ING3 is degraded by SCF(Skp2)-mediated ubiquitin-proteasome system

Oncogene
G ChenGang Li

Abstract

The inhibitor of growth family member 3 (ING3) has been shown to modulate transcription, cell cycle control and apoptosis. We previously reported that nuclear ING3 expression was remarkably reduced in melanomas, which correlated with a poorer patient survival, suggesting that decreased ING3 expression may be associated with melanoma progression. However, the mechanism of diminished ING3 expression in melanoma is not clear. Here we show that ING3 level was decreased in metastatic melanoma cells because of a rapid degradation. Furthermore, we showed that ING3 undergoes degradation through the ubiquitin-proteasome pathway. ING3 physically interacts with subunits of E3 ligase Skp1-Cullin-F-box protein complex (SCF complex). Knockdown of F-box protein S-phase kinase-associated protein 2 (Skp2) reduces the ubiquitination of ING3 and significantly stabilizes ING3 in melanoma cells. In addition, lysine 96 residue is essential for ING3 ubiquitination as its mutation to arginine dramatically abrogated ING3 degradation. Disruption of ING3 degradation stimulated ING3-induced G1 cell-cycle arrest and enhanced ultraviolet-induced apoptosis. Taken together, our data show that ING3 is degraded by the ubiquitin-proteasome pathway through the SC...Continue Reading

References

Feb 18, 2004·Molecular and Cellular Biology·Yannick DoyonJacques Côté
Apr 2, 2004·Trends in Cell Biology·Aaron Ciechanover, Ronen Ben-Saadon
Aug 4, 2004·Genes & Development·Mei-Ling KuoCharles J Sherr
Sep 10, 2004·Molecular Biology and Evolution·Gordon H Y HeKarl Riabowol
Sep 30, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Angelika M Burger, Arun K Seth
Oct 20, 2004·Journal of Cutaneous Pathology·Qing LiJ Andrew Carlson
Oct 20, 2004·Current Opinion in Plant Biology·Claus Schwechheimer, Luz Irina A Calderon Villalobos
Dec 22, 2004·The Journal of Investigative Dermatology·Kin Cheung P NgGang Li
Apr 20, 2005·Oncogene·Xiaolu L Ang, J Wade Harper
Jul 22, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Aparna Mani, Edward P Gelmann
Jul 30, 2005·International Journal of Cancer. Journal International Du Cancer·Hidetoshi SumimotoYutaka Kawakami
Feb 21, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hideto SonodaMasaki Mori
Mar 1, 2006·Journal of Dermatological Science·Yoshiyuki KatagiriShigeo Kondo
Mar 8, 2006·The Journal of Biological Chemistry·Yemin Wang, Gang Li
Mar 25, 2006·Future Oncology·Bruce R Zetter, Ursula Mangold
Apr 6, 2006·Journal of Biosciences·Dipankar NandiDilip Chandu
May 12, 2006·Journal of Cell Science·Anna von Mikecz
Jun 7, 2006·British Journal of Cancer·F LuG Li
Jul 4, 2006·Nature Reviews. Drug Discovery·Grzegorz NalepaJ Wade Harper
Jun 23, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marco GarateGang Li
Jul 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yemin WangGang Li
Jul 20, 2007·Endocrine-related Cancer·Gennaro ChiappettaGiuseppe Viglietto
Sep 21, 2007·Cancer Investigation·Kim Newton, Domagoj Vucic
Jan 29, 2008·Cardiovascular & Hematological Disorders Drug Targets·Imtiaz M Shah, Mario Di Napoli
May 27, 2008·Nature Reviews. Cancer·David Frescas, Michele Pagano
Sep 9, 2008·Experimental Cell Research·Kuo-Wang TsaiWen-Chang Lin

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Citations

Aug 14, 2010·Carcinogenesis·Alberto MorenoIgnacio Palmero
Mar 1, 2012·Pigment Cell & Melanoma Research·Carla A BrohemSilvya S Maria-Engler
Mar 3, 2010·Cellular and Molecular Life Sciences : CMLS·Brad Piche, Gang Li
Mar 19, 2014·FEBS Letters·Gesche Tallen, Karl Riabowol
Jun 8, 2012·The Journal of Investigative Dermatology·Guangdi ChenGang Li
Oct 3, 2015·Seminars in Cancer Biology·Yuan Liu, Rama K Mallampalli
Dec 18, 2013·Cancer Letters·Claire GuérillonRémy Pedeux
Aug 22, 2016·Journal of Cancer Research and Clinical Oncology·Runyun ZhangYongzhong Hou
May 3, 2012·Experimental Biology and Medicine·Hai-Yan YangLian-Xin Liu
Jan 31, 2018·British Journal of Cancer·Urszula L McClurgOlivier Binda
May 4, 2018·Biomedit︠s︡inskai︠a︡ khimii︠a︡·O A Buneeva, A E Medvedev
Jan 19, 2019·Oncology Letters·Xue-Feng YangHua-Chuan Zheng
Apr 30, 2017·Oncology Letters·Wen-Feng GouHua-Chuan Zheng
Jan 21, 2021·Frontiers in Oncology·Xiaoyan WuJingping Yuan
Sep 29, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ziwen ZhangXiaoli Wei
Jan 24, 2019·Cancer Letters·Marjorie GournayRémy Pedeux

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