C-terminal domain of SMYD3 serves as a unique HSP90-regulated motif in oncogenesis

Oncotarget
Mark A BrownHaley Tucker

Abstract

The SMYD3 histone methyl transferase (HMTase) and the nuclear chaperone, HSP90, have been independently implicated as proto-oncogenes in several human malignancies. We show that a degenerate tetratricopeptide repeat (TPR)-like domain encoded in the SMYD3 C-terminal domain (CTD) mediates physical interaction with HSP90. We further demonstrate that the CTD of SMYD3 is essential for its basal HMTase activity and that the TPR-like structure is required for HSP90-enhanced enzyme activity. Loss of SMYD3-HSP90 interaction leads to SMYD3 mislocalization within the nucleus, thereby losing its chromatin association. This results in reduction of SMYD3-mediated cell proliferation and, potentially, impairment of SMYD3's oncogenic activity. These results suggest a novel approach for blocking HSP90-driven malignancy in SMYD3-overexpressing cells with a reduced toxicity profile over current HSP90 inhibitors.

References

May 14, 1999·Trends in Biochemical Sciences·J Buchner
Oct 12, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G L Blatch, M Lässle
Feb 19, 2000·Current Opinion in Structural Biology·L H Pearl, C Prodromou
Aug 11, 2001·Science·T Jenuwein, C D Allis
Jul 12, 2002·Genesis : the Journal of Genetics and Development·Alexey VeraksaWilliam McGinnis
May 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Beili WuZihe Rao
Jul 6, 2004·Nature Cell Biology·Ryuji HamamotoYusuke Nakamura
Sep 22, 2005·Nature Reviews. Cancer·Luke Whitesell, Susan L Lindquist
Dec 29, 2005·International Journal of Cancer. Journal International Du Cancer·Bernd FrankBarbara Burwinkel
Jan 31, 2006·Cancer Science·Ryuji HamamotoYoichi Furukawa
Mar 11, 2006·Journal of Molecular Biology·Roberta SpadacciniMichael Sattler
Sep 11, 2007·Biochemical and Biophysical Research Communications·Mark A BrownPhilip W Tucker
Nov 7, 2007·Nature Structural & Molecular Biology·Sean D TavernaDinshaw J Patel
Jun 11, 2009·The Journal of Biological Chemistry·Hyunjung KimWoojin An
Jul 24, 2010·Nature Reviews. Cancer·Jane TrepelLen Neckers
Dec 15, 2010·Cell Stress & Chaperones·Rudi Kenneth Allan, Thomas Ratajczak
Sep 2, 2011·The Journal of Biological Chemistry·Li WangKehao Zhao
Oct 27, 2011·Journal of Molecular Cell Biology·Mohamed Abu-FarhaJean-François Couture
Dec 24, 2011·Cancer Research·Alicia M Cock-RadaJonathan B Weitzman
Mar 16, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Glenn S Van AllerRyan G Kruger
Aug 1, 2013·Pathology Oncology Research : POR·J M Patki, S S Pawar
Jan 7, 2014·Biochimica Et Biophysica Acta·Alejandra G ErlejmanMario D Galigniana

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Citations

Dec 27, 2016·Expert Opinion on Therapeutic Targets·Gurukumari RajajeyabalachandranSriram Rajagopal
Sep 22, 2019·Oncogene·Laurence DubrezCarmen Garrido
Apr 19, 2019·Future Medicinal Chemistry·Edoardo FabiniManuela Bartolini
Jan 5, 2017·AIMS Biophysics·Nicholas SpellmonZhe Yang
Aug 24, 2019·Digestive Diseases and Sciences·Cheng-Lin Zhu, Qiang Huang
Nov 19, 2019·Frontiers in Molecular Biosciences·Yingxue ZhangZhe Yang
Jan 16, 2020·Cancers·Cinzia BottinoGiuseppina Caretti
Dec 14, 2018·Nucleic Acids Research·Claudio FeniziaGiuseppina Caretti
Jan 6, 2021·Chembiochem : a European Journal of Chemical Biology·Vladimir O TalibovU Helena Danielson
Feb 28, 2021·Clinical Epigenetics·Benjamin J BernardVassiliki Saloura
Feb 13, 2018·Current Opinion in Physiology·Christopher TracySarah Franklin
Aug 8, 2019·Biochemistry·Edoardo FabiniU Helena Danielson
Dec 14, 2016·Journal of Chemical Information and Modeling·Balasubramanian Chandramouli, Giovanni Chillemi

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Methods Mentioned

BETA
transfection
immunoprecipitation
gel filtration

Software Mentioned

Sigmaplot
GeneEditor

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