Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Oct 6;64(1):176-188.
doi: 10.1016/j.molcel.2016.09.012.

Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1

Hitoshi Aihara  1 , Takeya Nakagawa  1 , Hirofumi Mizusaki  1 , Mitsuhiro Yoneda  1 , Masanori Kato  1 , Masamichi Doiguchi  1 , Yuko Imamura  1 , Miki Higashi  1 , Tsuyoshi Ikura  2 , Tomonori Hayashi  3 , Yoshiaki Kodama  3 , Masaya Oki  1 , Toshiyuki Nakayama  1 , Edwin Cheung  4 , Hiroyuki Aburatani  5 , Ken-Ichi Takayama  6 , Haruhiko Koseki  7 , Satoshi Inoue  6 , Yukio Takeshima  8 , Takashi Ito  9
Affiliations
Free article

Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1

Hitoshi Aihara et al. Mol Cell. .
Free article

Abstract

How deregulation of chromatin modifiers causes malignancies is of general interest. Here, we show that histone H2A T120 is phosphorylated in human cancer cell lines and demonstrate that this phosphorylation is catalyzed by hVRK1. Cyclin D1 was one of ten genes downregulated upon VRK1 knockdown in two different cell lines and showed loss of H2A T120 phosphorylation and increased H2A K119 ubiquitylation of its promoter region, resulting in impaired cell growth. In vitro, H2A T120 phosphorylation and H2A K119 ubiquitylation are mutually inhibitory, suggesting that histone phosphorylation indirectly activates chromatin. Furthermore, expression of a phosphomimetic H2A T120D increased H3 K4 methylation. Finally, both VRK1 and the H2A T120D mutant histone transformed NIH/3T3 cells. These results suggest that histone H2A T120 phosphorylation by hVRK1 causes inappropriate gene expression, including upregulated cyclin D1, which promotes oncogenic transformation.

Keywords: H2A; NHK-1; VRK1; cyclin D1; histone modification; phosphorylation; ubiquitylation.

PubMed Disclaimer

MeSH terms