Nickel compounds induce phosphorylation of histone H3 at serine 10 by activating JNK-MAPK pathway Export

@article{citeulike:2651052, abstract = {Nickel is a known carcinogen, although the mechanism of its carcinogenicity is not clear. Here, we provide evidence that nickel can induce phosphorylation of histone H3 at its serine 10 residue in a JNK/SAPK-dependent manner. Nickel induces the phosphorylation of c-Jun amino-terminal kinase (JNK), with no effect on the phosphorylation states of the ERK or p38 MAP kinases. An inhibitor of JNK eliminated the nickel-initiated JNK-mediated induction of histone H3 phosphorylation at serine 10, while inhibitors specific for ERK or p38 kinases had no effect on the phosphorylation levels of histone H3 at serine 10 (P-H3S10) in nickel-treated cells. A complete loss of Ni ion induced phosphorylation of H3S10 was observed when JNK was specifically knocked down with RNAi. These results are the first to show the specific JNK-mediated phosphorylation of histone H3 at its serine 10 residue. We show that addition of nickel to an in vitro P-H3S10 dephosphorylation reaction does not change the loss of phosphorylation in the reaction, supporting the notion that nickel causes H3S10 phosphorylation via the JNK/SAPK kinase pathway. It is likely that modification of histone H3 at serine 10 is one of a growing number of epigenetic changes believed to be involved in the carcinogenesis caused by nickel 10.1093/carcin/bgn084}, author = {Ke, Qingdong and Li, Qin and Ellen, Thomas P. and Sun, Hong and Costa, Max}, citeulike-article-id = {2651052}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/carcin/bgn084}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18375956}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18375956}, day = {28}, doi = {10.1093/carcin/bgn084}, journal = {Carcinogenesis}, keywords = {cancer, chromatin, epigenetics, histone, signalling, toxicology}, month = {March}, pages = {bgn084+}, posted-at = {2008-04-10 22:36:44}, priority = {5}, title = {Nickel compounds induce phosphorylation of histone H3 at serine 10 by activating JNK-MAPK pathway}, url = {http://dx.doi.org/10.1093/carcin/bgn084}, year = {2008} }

TY - JOUR ID - citeulike:2651052 L3 - citeulike-article-id:2651052 N2 - Nickel is a known carcinogen, although the mechanism of its carcinogenicity is not clear. Here, we provide evidence that nickel can induce phosphorylation of histone H3 at its serine 10 residue in a JNK/SAPK-dependent manner. Nickel induces the phosphorylation of c-Jun amino-terminal kinase (JNK), with no effect on the phosphorylation states of the ERK or p38 MAP kinases. An inhibitor of JNK eliminated the nickel-initiated JNK-mediated induction of histone H3 phosphorylation at serine 10, while inhibitors specific for ERK or p38 kinases had no effect on the phosphorylation levels of histone H3 at serine 10 (P-H3S10) in nickel-treated cells. A complete loss of Ni ion induced phosphorylation of H3S10 was observed when JNK was specifically knocked down with RNAi. These results are the first to show the specific JNK-mediated phosphorylation of histone H3 at its serine 10 residue. We show that addition of nickel to an in vitro P-H3S10 dephosphorylation reaction does not change the loss of phosphorylation in the reaction, supporting the notion that nickel causes H3S10 phosphorylation via the JNK/SAPK kinase pathway. It is likely that modification of histone H3 at serine 10 is one of a growing number of epigenetic changes believed to be involved in the carcinogenesis caused by nickel 10.1093/carcin/bgn084 JF - Carcinogenesis TI - Nickel compounds induce phosphorylation of histone H3 at serine 10 by activating JNK-MAPK pathway SP - bgn084 KW - cancer KW - chromatin KW - epigenetics KW - histone KW - signalling KW - toxicology AU - Ke, Qingdong AU - Li, Qin AU - Ellen, Thomas AU - Sun, Hong AU - Costa, Max PY - 2008/03/28/ UR - http://dx.doi.org/10.1093/carcin/bgn084 ER -