Phosphorylation of histone H2B serine 32 is linked to cell transformation

Andy T Y Lau, Sung Young Lee, Yan Ming Xu, Duo Zheng, Yong Yeon Cho, Feng Zhu, Hong Gyum Kim, Sheng Qing Li, Zhiguo Zhang, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Various types of post-translational modifications of the histone tails have been revealed, but a few modifications have been found within the histone core sequences. Histone core posttranslational modifications have the potential to modulate nucleosome structure and DNA accessibility. Here, we studied the histoneH2Bcore domain and found that phosphorylation of H2B serine 32 occurs in normal cycling and mitogen-stimulated cells. Notably, this phosphorylation is elevated in skin cancer cell lines and tissues compared with normal counterparts. The JB6 Cl41 mouse skin epidermal cell line is a well established model for tumor promoter-induced cell transformation and was used to study the function of H2B during EGF-induced carcinogenesis. Remarkably, cells overexpressing a nonphosphorylatable H2BS32A mutant exhibited suppressed growth and EGFinduced cell transformation, possibly because of decreased activation of activator protein-1, compared with control cells overexpressing wild type H2B. We identified ribosomal S6 kinase 2 (RSK2) as the kinase responsible for H2BS32 phosphorylation. Serum-starved JB6 cells contain very little endogenous H2BS32 phosphorylation, and EGF treatment induced this phosphorylation. The phosphorylation was attenuated in RSK2 knock-out MEFs and RSK2 knockdown JB6 cells. Taken together, our results demonstrate a novel role for H2B phosphorylation in cell transformation and show that H2BS32 phosphorylation is critical for controlling activator protein-1 activity, which is a major driver in cell transformation.

Original languageEnglish (US)
Pages (from-to)26628-26637
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number30
DOIs
StatePublished - Jul 29 2011

Fingerprint

Phosphorylation
Histones
Serine
Transcription Factor AP-1
Epidermal Growth Factor
Post Translational Protein Processing
Skin
Cells
Nucleosomes
Cell Line
Mitogens
Skin Neoplasms
Carcinogens
Phosphotransferases
Tail
Chemical activation
Carcinogenesis
Tissue
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lau, A. T. Y., Lee, S. Y., Xu, Y. M., Zheng, D., Cho, Y. Y., Zhu, F., ... Dong, Z. (2011). Phosphorylation of histone H2B serine 32 is linked to cell transformation. Journal of Biological Chemistry, 286(30), 26628-26637. https://doi.org/10.1074/jbc.M110.215590

Phosphorylation of histone H2B serine 32 is linked to cell transformation. / Lau, Andy T Y; Lee, Sung Young; Xu, Yan Ming; Zheng, Duo; Cho, Yong Yeon; Zhu, Feng; Kim, Hong Gyum; Li, Sheng Qing; Zhang, Zhiguo; Bode, Ann M.; Dong, Zigang.

In: Journal of Biological Chemistry, Vol. 286, No. 30, 29.07.2011, p. 26628-26637.

Research output: Contribution to journalArticle

Lau, ATY, Lee, SY, Xu, YM, Zheng, D, Cho, YY, Zhu, F, Kim, HG, Li, SQ, Zhang, Z, Bode, AM & Dong, Z 2011, 'Phosphorylation of histone H2B serine 32 is linked to cell transformation', Journal of Biological Chemistry, vol. 286, no. 30, pp. 26628-26637. https://doi.org/10.1074/jbc.M110.215590
Lau, Andy T Y ; Lee, Sung Young ; Xu, Yan Ming ; Zheng, Duo ; Cho, Yong Yeon ; Zhu, Feng ; Kim, Hong Gyum ; Li, Sheng Qing ; Zhang, Zhiguo ; Bode, Ann M. ; Dong, Zigang. / Phosphorylation of histone H2B serine 32 is linked to cell transformation. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 30. pp. 26628-26637.
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