Regulation of Ultraviolet B-induced Phosphorylation of Histone H3 at Serine 10 by Fyn Kinase

Abstract

Ultraviolet B (UVB) induces phosphorylation of histone H3 at serine 10, and mitogen-activated protein kinases are involved in this signal transduction pathway. Here we provide evidence that Fyn kinase, a member of the Src kinase family, is involved in the UVB-induced phosphorylation of histone H3 at serine 10. UVB distinctly increased Fyn kinase activity and phosphorylation. Fyn kinase inhibitors 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide and leflunomide, an Src kinase inhibitor, suppressed both UVB-induced phosphorylation of histone H3 at serine 10 and Fyn kinase activity and phosphorylation. UVB-induced phosphorylation of histone H3 at serine 10 was blocked by either a dominant-negative mutant of Fyn (DNM-Fyn) kinase or small interfering RNA of Fyn kinase. UVB-induced phosphorylation and activities of ERKs and protein kinase B/Akt were markedly inhibited by DNM-Fyn kinase. However, DNM-Fyn kinase did not inhibit UVB-induced phosphorylation of p38 MAPK or c-Jun N-terminal kinases. Active Fyn kinase phosphorylated histone H3 at serine 10 in vitro, and the phosphorylated Fyn kinase could translocate into the nucleus of HaCaT cells. These results indicate that Fyn kinase plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10. Ultraviolet B (UVB) induces phosphorylation of histone H3 at serine 10, and mitogen-activated protein kinases are involved in this signal transduction pathway. Here we provide evidence that Fyn kinase, a member of the Src kinase family, is involved in the UVB-induced phosphorylation of histone H3 at serine 10. UVB distinctly increased Fyn kinase activity and phosphorylation. Fyn kinase inhibitors 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide and leflunomide, an Src kinase inhibitor, suppressed both UVB-induced phosphorylation of histone H3 at serine 10 and Fyn kinase activity and phosphorylation. UVB-induced phosphorylation of histone H3 at serine 10 was blocked by either a dominant-negative mutant of Fyn (DNM-Fyn) kinase or small interfering RNA of Fyn kinase. UVB-induced phosphorylation and activities of ERKs and protein kinase B/Akt were markedly inhibited by DNM-Fyn kinase. However, DNM-Fyn kinase did not inhibit UVB-induced phosphorylation of p38 MAPK or c-Jun N-terminal kinases. Active Fyn kinase phosphorylated histone H3 at serine 10 in vitro, and the phosphorylated Fyn kinase could translocate into the nucleus of HaCaT cells. These results indicate that Fyn kinase plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10. Experimental evidence suggests that solar ultraviolet irradiation is the most important environmental carcinogen leading to the development of malignant skin melanoma (1Bode, A. M., and Dong, Z. (2003) Science STKE http://www.stke.org/cgi/content/fullOC_sigtrans;2003/RE2Google Scholar, 2Cleaver J.E. J. Dermatol. Sci. 2000; 23: 1-11Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 3Klein-Szanto A.J. Silvers W.K. Mintz B. Cancer Res. 1994; 54: 4569-4572PubMed Google Scholar). UV irradiation results in suppression of the immune system (4Beissert S. Hosoi J. Kuhn R. Rajewsky K. Muller W. Granstein R.D. J. Invest. Dermatol. 1996; 107: 553-557Abstract Full Text PDF PubMed Scopus (79) Google Scholar) and chronic skin damage including premature aging (5Fisher G.J. Datta S.C. Talwar H.S. Wang Z.Q. Varani J. Kang S. Voorhees J.J. Nature. 1996; 379: 335-339Crossref PubMed Scopus (1198) Google Scholar). According to wavelength, UV is divided into UVA 1The abbreviations used are: UVA, ultraviolet A; ERKs, extracellular signal-regulated kinases; PTKs, protein tyrosine kinases; MEM, minimal essential medium; FBS, fetal bovine serum; MSKs, mitogen- and stress-activated protein kinases; GSK, glycogen synthase kinase; PVDF, polyvinylidene difluoride; PBS, phosphate-buffered saline; UVB, ultraviolet B; siRNA, small interfering RNA; PP2, 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide; DNM-Fyn, dominant-negative mutant of Fyn; DMEM, Dulbecco's modified Eagle's medium; WT, wild type; MAP, mitogen-activated protein; IKK, IκB kinase. (UVA I, 340–400 nm; UVA II (320–340 nm), UVB (280–320 nm), and UVC (180–280 nm). UVA and UVB are recognized as the chief carcinogenic components of sunlight with relevance to human skin cancer (1Bode, A. M., and Dong, Z. (2003) Science STKE http://www.stke.org/cgi/content/fullOC_sigtrans;2003/RE2Google Scholar, 2Cleaver J.E. J. Dermatol. Sci. 2000; 23: 1-11Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). UVB irradiation has the ability to stimulate oncogene c-fos promoter expression (6Gonzales M. Bowden G.T. Gene (Amst.). 2002; 293: 169-179Crossref PubMed Scopus (34) Google Scholar), to accumulate c-fos mRNA and c-Fos protein, and to increase activator protein-1 activation (7Chen W. Borchers A.H. Dong Z. Powell M.B. Bowden G.T. J. Biol. Chem. 1998; 273: 32176-32181Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar). In addition, it also induces tumor suppressor p53 (8Chazal M. Marionnet C. Michel L. Mollier K. Dazard J.E. Della Valle V. Larsen C.J. Gras M.P. Basset-Seguin N. Oncogene. 2002; 21: 2652-2661Crossref PubMed Scopus (33) Google Scholar, 9Pedeux R. Lefort K. Cuenin C. Cortes U. Kellner K. Dore J.F. Nakazawa H. Int. J. Cancer. 2002; 98: 811-816Crossref PubMed Scopus (19) Google Scholar, 10Latonen L. Taya Y. Laiho M. Oncogene. 2001; 20: 6784-6793Crossref PubMed Scopus (110) Google Scholar) and p16 (INK4A-ARF) expression (8Chazal M. Marionnet C. Michel L. Mollier K. Dazard J.E. Della Valle V. Larsen C.J. Gras M.P. Basset-Seguin N. Oncogene. 2002; 21: 2652-2661Crossref PubMed Scopus (33) Google Scholar). By using oligonucleotide microarray analysis, researchers found that several biological processes, including basal transcription, splicing, and translation, as well as proteasome-mediated degradation, are globally affected by UVB irradiation in human keratinocytes (11Sesto A. Navarro M. Burslem F. Jorcano J.L. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 2965-2970Crossref PubMed Scopus (161) Google Scholar). These results demonstrate the complexity of the UVB response. Various signal transduction pathways, including extracellular signal-regulated kinases (ERKs), p38 kinase, and c-Jun N-terminal kinases (JNKs), are involved in UVB-induced cell proliferation or apoptosis (1Bode, A. M., and Dong, Z. (2003) Science STKE http://www.stke.org/cgi/content/fullOC_sigtrans;2003/RE2Google Scholar, 7Chen W. Borchers A.H. Dong Z. Powell M.B. Bowden G.T. J. Biol. Chem. 1998; 273: 32176-32181Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar, 12She Q.B. Ma W.Y. Zhong S. Dong Z. J. Biol. Chem. 2002; 277: 24039-24048Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 13Nomura M. Kaji A. He Z. Ma W.Y. Miyamoto K. Yang C.S. Dong Z. J. Biol. Chem. 2001; 276: 46624-46631Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, 14She Q.B. Ma W.Y. Dong Z. Oncogene. 2002; 21: 1580-1589Crossref PubMed Scopus (58) Google Scholar). We recently found that UVB induces phosphorylation of histone H3 at serine 10 or serine 28 through MAP kinases or mitogen- and stress-activated protein kinase 1 (MSK1) (15Zhong S. Zhang Y. Jansen C. Goto H. Inagaki M. Dong Z. J. Biol. Chem. 2001; 276: 12932-12937Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 16Zhong S.P. Ma W.Y. Dong Z. J. Biol. Chem. 2000; 275: 20980-20984Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). However, much less is known about the UVB-induced phosphorylation of histone H3, especially the upstream mediators in the signal transduction pathway of UVB irradiation. Modification of histones is an important element in the regulation of gene expression, and histone H3 phosphorylation at serine 10 has traditionally been regarded as a marker for mitosis (17Bradbury E.M. BioEssays. 1992; 14: 9-16Crossref PubMed Scopus (347) Google Scholar, 18Gurley L.R. D'Anna J.A. Barham S.S. Deaven L.L. Tobey R.A. Eur. J. Biochem. 1978; 84: 1-15Crossref PubMed Scopus (404) Google Scholar). Increased phosphorylation of histone H3 at serine 10 was found in mitogen-stimulated and oncogene-transformed mouse fibroblasts (19Chadee D.N. Hendzel M.J. Tylipski C.P. Allis C.D. Bazett-Jones D.P. Wright J.A. Davie J.R. J. Biol. Chem. 1999; 274: 24914-24920Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar). Phosphorylation of H3 at serine 10 corresponds with chromatin relaxation and gene expression in interphase, whereas in mitosis it is associated with chromosome condensation (20Prigent C. Dimitrov S. J. Cell Sci. 2003; 116: 3677-3685Crossref PubMed Scopus (365) Google Scholar). Thus to identify the responsible kinases and the circumstances under which histone H3 at serine 10 becomes phosphorylated is important. Fyn kinase is a member of the Src family of nonreceptor protein-tyrosine kinases and is associated with outgrowth during development and regeneration of the central and peripheral nervous systems (21Maness P.F. Dev. Neurosci. 1992; 14: 257-270Crossref PubMed Scopus (64) Google Scholar, 22Bhat N.R. Dev. Neurosci. 1995; 17: 267-284Crossref PubMed Scopus (40) Google Scholar). Fyn kinase can interact with numerous other signal molecules, and it has diverse biological functions including signaling via the T cell receptor, regulation of brain function, and adhesion-mediated signaling (23Resh M.D. Int. J. Biochem. Cell Biol. 1998; 30: 1159-1162Crossref PubMed Scopus (111) Google Scholar). Recent research indicates that Fyn kinase is expressed in T cells, and it is the first signaling molecule to be activated downstream of the T cell receptor (24Zamoyska R. Basson A. Filby A. Legname M. B. 2003; PubMed Scopus Google Scholar). Fyn kinase is also involved in receptor signaling and the of the at and and A. M. L. J. Cell Biol. 2001; PubMed Scopus Google Scholar). In and evidence that Src kinase family interact with MAP kinases in to activation of MAP kinase by an Src family kinase and that downstream of protein kinase in the cell M. M. V. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). activation is by Src kinase M. J. J. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar), and kinase via Fyn kinase J. M. M. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar). Src kinases interact with kinases are to a of the of UVB-induced we used UVB to phosphorylation of histone H3 at serine 10. We found that UVB phosphorylation of histone H3 at serine 10 in a and and increased Fyn kinase Fyn kinase and leflunomide, an Src kinase inhibitor, inhibited UVB-induced Fyn kinase activity and phosphorylation of histone H3 at serine 10 in a Fyn kinase and Fyn kinase UVB-induced phosphorylation of histone H3 at serine 10. DNM-Fyn kinase inhibited UVB-induced ERKs and activities and phosphorylation. indicates that Fyn kinase plays a key role in UVB-induced phosphorylation of histone H3 at serine 10 through regulation of and minimal essential and were of and mutant were by for Cancer to phosphorylation of histone at serine 10 and histone H3 protein, phosphorylation of ERKs, p38 MAP kinase, and and kinase were was bovine was was kinase and ERKs kinase were Cell was and and modified protein were and for of Fyn kinase were by Cell mouse cell dominant-negative kinase, and wild Fyn were as in with and at in a of HaCaT were in with and at in a of of UVB were and with phosphate-buffered of the was to the by were the and at at for 10 were with and with 10 of 10 and was to a of and were for were at for 10 at in a and the were were to and for at a of were at for 10 at and the were with and with were in and at was to the in the modified protein of H3 at of histone H3 at serine 10 was as Z. Ma W.Y. Zhang Y. Dong Z. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). In a phosphorylation of histone H3 at serine 10 or histone H3 was to the UVB-induced phosphorylation of histone H3 at serine 10 using a were with and using the the using and mutant we to the of were in for and the was to and were for phosphorylation and activity of Fyn kinase. ability of DNM-Fyn kinase to inhibit the UVB-induced phosphorylation of was by using an kinase In were with UVB at for the were with the and of cell 1 was to and the were and to were for and for 10 at and the were to other Cell protein and with were by for at These were for 1 at and with of cell and with of kinase were in of kinase with and of protein and for at was with 10 of were at for were by were to and kinase activity was by using a ERKs MAP ability of DNM-Fyn kinase to inhibit UVB-induced phosphorylation of ERKs was using a MAP kinase and of were as Cell protein and MAP kinase were by for at These were and were in kinase with and protein and for at was with 10 of were at for were by were to and kinases activity was by using a Fyn activation of Fyn kinase was by a In of cell protein were with in for 1 at was at for at and the was to and for at These were and were in of kinase with 10 of and of Src and for at was and with for and with for was by were RNA Fyn and the Cell the role of Fyn kinase in the regulation of phosphorylation of histone H3 at serine 10, we kinase expression by the oligonucleotide of Fyn kinase used for was and the is In the the indicate a and the RNA In the the an of was into the and were as Proc. Natl. Acad. Sci. U. S. A. 2002; 99: PubMed Scopus Google Scholar). oligonucleotide and of the in the were by with the Fyn kinase and is and were into using the were with as and Fyn kinase expression was by a using an kinase Active Fyn H3 at 10 in Phosphorylation of histone H3 by Fyn kinase was to the In of histone H3 was for 1 at with the Fyn kinase and in of kinase 10 were to 10 of and by phosphorylation of histone H3 at serine 10 and histone H3 protein were by with Fyn were and in for were in for or UVB irradiation and were to and protein was by the modified protein Fyn kinase was by using a Fyn that the did not with the protein, was also by using an protein was by the of UVB Phosphorylation of H3 at 10 in a and keratinocytes were human and to cell and it is an cell for the of UVB human skin M. Bowden G.T. Oncogene. 2002; 21: PubMed Scopus Google Scholar, M. L. B. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). In this HaCaT were used to the UVB-induced phosphorylation of histone H3 at serine 10. that phosphorylation of histone H3 at serine 10 to with UVB of histone H3 protein did not that phosphorylation of histone H3 with of UVB or with histone H3 protein These results indicate that phosphorylation of histone H3 at serine 10 is by UVB in a and UVB Fyn and Phosphorylation of Fyn at results also that UVB Fyn kinase activity in a and We found that a increase in Fyn kinase activity in with Fyn kinase activity a were with 1 of UVB, and to a of we that of UVB distinctly phosphorylation of histone H3 at serine 28 or serine 10 in (15Zhong S. Zhang Y. Jansen C. Goto H. Inagaki M. Dong Z. J. Biol. Chem. 2001; 276: 12932-12937Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 16Zhong S.P. Ma W.Y. Dong Z. J. Biol. Chem. 2000; 275: 20980-20984Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar), a of of UVB was used to the of UVB phosphorylation of Fyn kinase also in a and and and kinase was B and phosphorylation of Fyn kinase in a and HaCaT were with UVB and or were and the phosphorylation of Fyn kinase was by using a with a kinase HaCaT were with the of UVB, and phosphorylation of Fyn kinase at was by as of Fyn kinase protein was by using a kinase and Fyn UVB-induced Phosphorylation of H3 at indicate that UVB induces phosphorylation of histone H3 at serine 10 and induces Fyn kinase we that Fyn kinase a key role in the UVB-induced phosphorylation of histone H3 at serine 10, and H3 phosphorylation be by of Fyn kinase. In this we found that PP2, a Fyn kinase R. F. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), and leflunomide, an Src kinase A. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar), markedly inhibited the UVB-induced phosphorylation of histone H3 at serine 10 in a and did not the histone H3 protein B and not also indicates that Fyn kinase plays an important role in UVB-induced phosphorylation of histone H3 at serine 10. Fyn Fyn and Fyn kinase inhibitors markedly suppressed UVB-induced phosphorylation of histone H3 at serine 10, we inhibitors can Fyn kinase activity and phosphorylation under the We found that either or inhibited UVB-induced Fyn kinase activity and phosphorylation in a Fyn UVB-induced Phosphorylation of H3 at the role of Fyn kinase in UVB-induced phosphorylation of histone H3 at serine 10, we used DNM-Fyn and to expressed DNM-Fyn and cells. that phosphorylation of histone H3 at serine 10 by UVB was inhibited in the histone H3 protein did not DNM-Fyn also distinctly inhibited UVB-induced phosphorylation of Fyn kinase the Fyn kinase protein was also These results indicate that Fyn kinase plays a important role in the phosphorylation of histone H3 at serine 10 by RNA Fyn UVB-induced Phosphorylation of H3 at also used the to the Fyn kinase expression and we the UVB-induced phosphorylation of histone H3 at serine 10. we the of for Fyn kinase using and an results that the Fyn kinase protein to of that in protein was used to protein in well These results indicate that the kinase well in results that UVB increased phosphorylation of histone H3 at serine 10 in the not in the in a and and histone H3 were and Fyn UVB-induced Phosphorylation of and ERKs kinase is involved in UVB-induced phosphorylation of histone H3 at serine the signal transduction components by Fyn kinase leading to that phosphorylation are We that Fyn kinase is upstream of the known signal transduction and Fyn kinase can several downstream which are into the nucleus histone H3 in We the of several MAP kinases and phosphorylation in and DNM-Fyn cells. We found that UVB ERKs and phosphorylation and not p38 MAP kinase or and in cells. ERKs and were not affected by UVB in DNM-Fyn cells. protein of p38 MAP kinase, ERKs, and were in either cell and DNM-Fyn and ERKs the results we activity of ERKs and in and DNM-Fyn cells. and MAP kinase was used to for activity and ERKs kinase was and the ERKs was results that phosphorylation of and in protein of was Phosphorylation of in with and protein was These that DNM-Fyn kinase also inhibited UVB-induced and ERKs Active Fyn H3 at 10 in we Fyn kinase could histone H3 at serine 10 in We used histone H3 protein as the Fyn kinase and we it with Fyn kinase and phosphorylation of histone H3 at serine 10 by results that Fyn kinase phosphorylated histone H3 at serine 10 in in a was used to the of histone H3 protein was These indicate that Fyn kinase can the histone H3 protein at serine 10 in Fyn into the Fyn kinase can histone H3 in we first that the phosphorylated Fyn kinase can be to the nucleus the in HaCaT cells. UVB phosphorylated Fyn kinase increased in both the and nucleus that the were not with the were by using an is known to be found in the and not in the results that was in the that the was not with of was by expression These results that phosphorylated Fyn kinase also can be to the nucleus to other kinases. Fyn kinase is a member of the Src family of tyrosine and it has diverse biological including signaling via the T cell receptor, regulation of brain function, and signaling (21Maness P.F. Dev. Neurosci. 1992; 14: 257-270Crossref PubMed Scopus (64) Google Scholar, 22Bhat N.R. Dev. Neurosci. 1995; 17: 267-284Crossref PubMed Scopus (40) Google Scholar, M.D. Int. J. Biochem. Cell Biol. 1998; 30: 1159-1162Crossref PubMed Scopus (111) Google Scholar, R. Basson A. Filby A. Legname M. B. 2003; PubMed Scopus Google Scholar). In the we found that Fyn kinase plays a key role in the regulation of UVB-induced phosphorylation of histone H3 at serine 10. that UVB induces phosphorylation of histone H3 at serine 10 or serine 28 in cells, which is through MAP kinases or mitogen- and stress-activated protein kinase (MSK1) (15Zhong S. Zhang Y. Jansen C. Goto H. Inagaki M. Dong Z. J. Biol. Chem. 2001; 276: 12932-12937Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 16Zhong S.P. Ma W.Y. Dong Z. J. Biol. Chem. 2000; 275: 20980-20984Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). However, is known about the upstream mediators in UVB-induced phosphorylation of histone the carcinogenic of UVB and the of UVB-induced phosphorylation of histone H3 at serine 10, we used the HaCaT cell HaCaT cell is a human cell human and it J. A. J. Cell Biol. PubMed Scopus Google Scholar). cell is and has a in a human J. A. J. Cell Biol. PubMed Scopus Google Scholar). indicates that of UVB a of and c-fos in HaCaT Z. M. R. W. J.R. J. Dermatol. Full Text PDF PubMed Scopus Google Scholar). Here we found that UVB phosphorylation of histone H3 at serine 10 in human HaCaT in a and UVB also markedly increased Fyn kinase activity and phosphorylation in a and that UVB irradiation results in the of the activator protein-1 in HaCaT and increased c-fos and expression Davie J.R. Cancer Res. 2002; Google Scholar). gene expression including that of the c-fos is associated with phosphorylation of histone H3 at serine 10 Davie J.R. Cancer Res. 2002; Google Scholar, S. M.J. J. 2000; PubMed Scopus Google Scholar). results indicate that UVB induces phosphorylation of histone H3 at serine 10 in the human HaCaT cell and Fyn kinase activity plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10. that Fyn kinase is involved in UVB-induced phosphorylation of histone H3 at serine 10, PP2, a Fyn kinase R. F. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), and leflunomide, an Src family kinase A. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar), were to Fyn kinase indicate that and inhibited UVB-induced phosphorylation of histone H3 at serine 10 in a the and also inhibited UVB-induced Fyn kinase activity and phosphorylation at These results that Fyn kinase is involved in phosphorylation of histone H3 at serine 10. of we and DNM-Fyn into cells, which are mouse skin and are a well cell for tumor Z. M.J. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar, Nature. PubMed Scopus Google Scholar). In the we found that Fyn inhibited UVB-induced phosphorylation of Fyn kinase at and phosphorylation of histone H3 at serine 10 by UVB we the of Fyn kinase in UVB-induced phosphorylation of histone H3 at serine 10 by the results that UVB-induced phosphorylation of histone H3 was also inhibited by Fyn kinase with with the and Fyn kinase has Fyn is of the involved in during development H. S. S. Nature. 1994; PubMed Scopus Google Scholar), and of activation of Fyn tyrosine kinase A. M.D. J. Cell Biol. 1999; PubMed Scopus Google Scholar). Here results indicate that Fyn kinase is a key in the UVB-induced phosphorylation of histone H3 at serine 10. the of Fyn kinase in the regulation of phosphorylation of histone H3 at serine 10, we the phosphorylation of other kinases. of kinases are associated with phosphorylation of histone H3 at serine 10 (15Zhong S. Zhang Y. Jansen C. Goto H. Inagaki M. Dong Z. J. Biol. 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N. M. Oncogene. 2001; 20: PubMed Scopus Google Scholar). Fyn kinase UVB-induced phosphorylation of histone H3 at serine 10 also through the pathway. that Fyn kinase is involved in UVB-induced phosphorylation of histone H3 at serine 10 and that Fyn kinase is important that the UVB-induced phosphorylation of histone H3 at serine 10. UVB also induces phosphorylation of histone H3 at serine 10 through a p38 MAP kinase pathway (15Zhong S. Zhang Y. Jansen C. Goto H. Inagaki M. Dong Z. J. Biol. Chem. 2001; 276: 12932-12937Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar) evidence that a of UVB in in and However, including UVB into cells, to be We Cancer with Fyn kinase and dominant-negative mutant Fyn kinase and we also for