Apoptotic Phosphorylation of Histone H3 on Ser-10 by Protein Kinase Cδ

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Sep 18

PMID 22984491

Citations 24

Authors

Choon-Ho Park

Kyong-Tai Kim

Affiliations

Soon will be listed here.

Abstract

Phosphorylation of histone H3 on Ser-10 is regarded as an epigenetic mitotic marker and is tightly correlated with chromosome condensation during both mitosis and meiosis. However, it was also reported that histone H3 Ser-10 phosphorylation occurs when cells are exposed to various death stimuli, suggesting a potential role in the regulation of apoptosis. Here we report that histone H3 Ser-10 phosphorylation is mediated by the pro-apoptotic kinase protein kinase C (PKC) δ during apoptosis. We observed that PKCδ robustly phosphorylates histone H3 on Ser-10 both in vitro and in vivo. Ectopic expression of catalytically active PKCδ efficiently induces condensed chromatin structure in the nucleus. We also discovered that activation of PKCδ is required for histone H3 Ser-10 phosphorylation after treatment with DNA damaging agents during apoptosis. Collectively, these findings suggest that PKCδ is the kinase responsible for histone H3 Ser-10 phosphoryation during apoptosis and thus contributes to chromatin condensation together with other apoptosis-related histone modifications. As a result, histone H3 Ser-10 phosphorylation can be designated a new 'apoptotic histone code' mediated by PKCδ.

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References

Goto H, Tomono Y, Ajiro K, Kosako H, Fujita M, Sakurai M . Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. J Biol Chem. 1999; 274(36):25543-9. DOI: 10.1074/jbc.274.36.25543. View

Cheung W, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen C . Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell. 2003; 113(4):507-17. DOI: 10.1016/s0092-8674(03)00355-6. View

Mecklenbrauker I, Kalled S, Leitges M, Mackay F, Tarakhovsky A . Regulation of B-cell survival by BAFF-dependent PKCdelta-mediated nuclear signalling. Nature. 2004; 431(7007):456-61. DOI: 10.1038/nature02955. View

Ghayur T, Hugunin M, Talanian R, Ratnofsky S, Quinlan C, Emoto Y . Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis. J Exp Med. 1996; 184(6):2399-404. PMC: 2196396. DOI: 10.1084/jem.184.6.2399. View

Park C, Choi B, Jeong M, Kim S, Kim W, Song Y . Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage-induced apoptosis. Mol Biol Cell. 2011; 22(8):1398-408. PMC: 3078082. DOI: 10.1091/mbc.E10-08-0717. View

Baek S . When signaling kinases meet histones and histone modifiers in the nucleus. Mol Cell. 2011; 42(3):274-84. DOI: 10.1016/j.molcel.2011.03.022. View

Goto H, Yasui Y, Nigg E, Inagaki M . Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes Cells. 2002; 7(1):11-7. DOI: 10.1046/j.1356-9597.2001.00498.x. View

Strahl B, Allis C . The language of covalent histone modifications. Nature. 2000; 403(6765):41-5. DOI: 10.1038/47412. View

Prigent C, Dimitrov S . Phosphorylation of serine 10 in histone H3, what for?. J Cell Sci. 2003; 116(Pt 18):3677-85. DOI: 10.1242/jcs.00735. View

10.

Bode A, Dong Z . Inducible covalent posttranslational modification of histone H3. Sci STKE. 2005; 2005(281):re4. DOI: 10.1126/stke.2812005re4. View

11.

Dai J, Sultan S, Taylor S, Higgins J . The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev. 2005; 19(4):472-88. PMC: 548948. DOI: 10.1101/gad.1267105. View

12.

Perez-Cadahia B, Drobic B, Khan P, Shivashankar C, Davie J . Current understanding and importance of histone phosphorylation in regulating chromatin biology. Curr Opin Drug Discov Devel. 2010; 13(5):613-22. View

13.

Griner E, Kazanietz M . Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer. 2007; 7(4):281-94. DOI: 10.1038/nrc2110. View

14.

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

15.

Wang D, Lippard S . Cisplatin-induced post-translational modification of histones H3 and H4. J Biol Chem. 2004; 279(20):20622-5. DOI: 10.1074/jbc.M402547200. View

16.

Campos E, Reinberg D . Histones: annotating chromatin. Annu Rev Genet. 2009; 43:559-99. DOI: 10.1146/annurev.genet.032608.103928. View

17.

Nowak S, Corces V . Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. Trends Genet. 2004; 20(4):214-20. DOI: 10.1016/j.tig.2004.02.007. View

18.

Waring P, Khan T, Sjaarda A . Apoptosis induced by gliotoxin is preceded by phosphorylation of histone H3 and enhanced sensitivity of chromatin to nuclease digestion. J Biol Chem. 1997; 272(29):17929-36. DOI: 10.1074/jbc.272.29.17929. View

19.

Fullgrabe J, Hajji N, Joseph B . Cracking the death code: apoptosis-related histone modifications. Cell Death Differ. 2010; 17(8):1238-43. DOI: 10.1038/cdd.2010.58. View

20.

Hu Y, Liu Z, Yang S, Ye K . Acinus-provoked protein kinase C delta isoform activation is essential for apoptotic chromatin condensation. Cell Death Differ. 2007; 14(12):2035-46. DOI: 10.1038/sj.cdd.4402214. View