Article abstract
Nature Cell Biology 6, 731 - 740 (2004)
Published online: 4 July 2004 | doi:10.1038/ncb1151
SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells
Ryuji Hamamoto1, Yoichi Furukawa1, Masashi Morita2, Yuko Iimura2, Fabio Pittella Silva1, Meihua Li1, Ryuichiro Yagyu1 & Yusuke Nakamura1
Abstract
Colorectal and hepatocellular carcinomas are some of the leading causes of cancer deaths worldwide, but the mechanisms that underly these malignancies are not fully understood. Here we report the identification of SMYD3, a gene that is over-expressed in the majority of colorectal carcinomas and hepatocellular carcinomas. Introduction of SMYD3 into NIH3T3 cells enhanced cell growth, whereas genetic knockdown with small-interfering RNAs (siRNAs) in cancer cells resulted in significant growth suppression. SMYD3 formed a complex with RNA polymerase II through an interaction with the RNA helicase HELZ and transactivated a set of genes that included oncogenes, homeobox genes and genes associated with cell-cycle regulation. SMYD3 bound to a motif, 5'-CCCTCC-3', present in the promoter region of downstream genes such as Nkx2.8. The SET domain of SMYD3 showed histone H3-lysine 4 (H3-K4)-specific methyltransferase activity, which was enhanced in the presence of the heat-shock protein HSP90A. Our findings suggest that SMYD3 has histone methyltransferase activity and plays an important role in transcriptional regulation as a member of an RNA polymerase complex. Furthermore, activation of SMYD3 may be a key factor in human carcinogenesis.
- Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
- Banyu Tsukuba Research Institute, 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan.
Correspondence to: Yusuke Nakamura1 e-mail: yusuke@ims.u-tokyo.ac.jp
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Methyl magic and HAT tricksNature Structural Biology News and Views (01 Dec 2002)
Histone methylation unSETtledNature Structural Biology News and Views (01 Apr 2003)
See all 6 matches for News And ViewsRESEARCH
Plasmid-chromosome shuffling for non-deletion alleles in yeastNature Methods Brief Communication (01 Feb 2008)
The Huntington's disease candidate region exhibits many different haplotypesNature Genetics Article (01 May 1992)
See all 65 matches for Research
