Apoptotic Histone Modification Inhibits Nuclear Transport by Regulating RCC1

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2008 Dec 9

PMID 19060893

Citations 26

Authors

Chi-Hang Wong

Hei Chan

Chin-Yee Ho

Soak-Kuan Lai

Kheng-Sze Chan

Cheng-Gee Koh

Hoi-Yeung Li

Affiliations

Soon will be listed here.

Abstract

A number of signalling pathways have been identified that regulate apoptosis, but the mechanism that initiates apoptosis remains incompletely understood. We have found that the nuclear RanGTP level is diminished during the early stages of apoptosis, which correlates with immobilization of RCC1 on the chromosomes. Furthermore, the expression of phosphomimetic histone H2B or caspase-activated Mst1 immobilizes RCC1 and causes reduction of nuclear RanGTP levels, which leads to inactivation of the nuclear transport machinery. As a consequence, nuclear localization signal (NLS)-containing proteins, including NF-kappaB-p65, remain bound to importins alpha and beta in the cytoplasm. Knocking down Mst1 allows resumption of nuclear transport and the nuclear entry of NF-kappaB-p65, which have important roles in rescuing cells from apoptosis. Therefore, we propose that RCC1 reads the histone code created by caspase-activated Mst1 to initiate apoptosis by reducing the level of RanGTP in the nucleus.

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References

Phair R, Misteli T . High mobility of proteins in the mammalian cell nucleus. Nature. 2000; 404(6778):604-9. DOI: 10.1038/35007077. View

Cushman I, Stenoien D, Moore M . The dynamic association of RCC1 with chromatin is modulated by Ran-dependent nuclear transport. Mol Biol Cell. 2003; 15(1):245-55. PMC: 307544. DOI: 10.1091/mbc.e03-06-0409. View

Kihlmark M, Rustum C, Eriksson C, Beckman M, Iverfeldt K, Hallberg E . Correlation between nucleocytoplasmic transport and caspase-3-dependent dismantling of nuclear pores during apoptosis. Exp Cell Res. 2004; 293(2):346-56. DOI: 10.1016/j.yexcr.2003.10.019. View

Li H, Zheng Y . Phosphorylation of RCC1 in mitosis is essential for producing a high RanGTP concentration on chromosomes and for spindle assembly in mammalian cells. Genes Dev. 2004; 18(5):512-27. PMC: 374234. DOI: 10.1101/gad.1177304. View

Kihlmark M, Imreh G, Hallberg E . Sequential degradation of proteins from the nuclear envelope during apoptosis. J Cell Sci. 2001; 114(Pt 20):3643-53. DOI: 10.1242/jcs.114.20.3643. View

Ahn S, Cheung W, Hsu J, Diaz R, Smith M, Allis C . Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005; 120(1):25-36. DOI: 10.1016/j.cell.2004.11.016. View

Misteli T, Gunjan A, Hock R, Bustin M, Brown D . Dynamic binding of histone H1 to chromatin in living cells. Nature. 2000; 408(6814):877-81. DOI: 10.1038/35048610. View

de Souza P, Lindsay M . Mammalian Sterile20-like kinase 1 and the regulation of apoptosis. Biochem Soc Trans. 2004; 32(Pt3):485-8. DOI: 10.1042/BST0320485. View

Li H, Wirtz D, Zheng Y . A mechanism of coupling RCC1 mobility to RanGTP production on the chromatin in vivo. J Cell Biol. 2003; 160(5):635-44. PMC: 2173367. DOI: 10.1083/jcb.200211004. View

10.

Fagerlund R, Kinnunen L, Kohler M, Julkunen I, Melen K . NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4. J Biol Chem. 2005; 280(16):15942-51. DOI: 10.1074/jbc.M500814200. View

11.

Walther T, Fornerod M, Pickersgill H, Goldberg M, ALLEN T, Mattaj I . The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins. EMBO J. 2001; 20(20):5703-14. PMC: 125666. DOI: 10.1093/emboj/20.20.5703. View

12.

Renault L, Kuhlmann J, Henkel A, Wittinghofer A . Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell. 2001; 105(2):245-55. DOI: 10.1016/s0092-8674(01)00315-4. View

13.

Uchida S, Sekiguchi T, Nishitani H, Miyauchi K, Ohtsubo M, Nishimoto T . Premature chromosome condensation is induced by a point mutation in the hamster RCC1 gene. Mol Cell Biol. 1990; 10(2):577-84. PMC: 360843. DOI: 10.1128/mcb.10.2.577-584.1990. View

14.

Nomura M, Shimizu S, Ito T, Narita M, Matsuda H, Tsujimoto Y . Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res. 1999; 59(21):5542-8. View

15.

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

16.

Bischoff F, Ponstingl H . Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature. 1991; 354(6348):80-2. DOI: 10.1038/354080a0. View

17.

Glantschnig H, Rodan G, Reszka A . Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation. J Biol Chem. 2002; 277(45):42987-96. DOI: 10.1074/jbc.M208538200. View

18.

Faleiro L, Lazebnik Y . Caspases disrupt the nuclear-cytoplasmic barrier. J Cell Biol. 2000; 151(5):951-9. PMC: 2174353. DOI: 10.1083/jcb.151.5.951. View

19.

Karpova T, Baumann C, He L, Wu X, Grammer A, Lipsky P . Fluorescence resonance energy transfer from cyan to yellow fluorescent protein detected by acceptor photobleaching using confocal microscopy and a single laser. J Microsc. 2003; 209(Pt 1):56-70. DOI: 10.1046/j.1365-2818.2003.01100.x. View

20.

Bischoff F, Ponstingl H . Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. Proc Natl Acad Sci U S A. 1991; 88(23):10830-4. PMC: 53025. DOI: 10.1073/pnas.88.23.10830. View