Phosphorylation of histone H3 at Ser10: its role in cell transformation by v-Src.
We found that transformation by v-src constitutively activated phosphorylation of histone H3 at Ser10 in a transformation-specific manner. While nontransforming mutant of v-src did not activate H3 phosphorylation, H3 phosphorylation in cells expressing temperature-sensitive mutant of v-src was temperature-dependent. Inhibition of Ras signaling by Gap1m, a GTPase-activation protein for Ras, or S17N Ras, a dominant negative form of Ras, substantially suppressed the Ser10 phosphorylation of H3. Similarly, treatment of cells with manumycin A, a potent inhibitor of Ras-falnesyl transferase, clearly suppressed the H3 phosphorylation. In contrast, inhibition of STAT3 signaling or PI3K signaling did not perturb H3 phosphorylation. We found, however, inhibition of MEK or MSK1 markedly suppressed H3 phosphorylation. In addition, inhibition of MSK1 expression by its siRNA substantially suppressed H3 phosphorylation and anchorage-independent growth of transformed cells. Taken together, our results strongly suggest the importance of MSK1 and H3 phosphorylation in cell transformation by v-Src.
Tange
Shoichiro
S
Division of Cancer Biology, Department of Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Ito
Satoko
S
Senga
Takeshi
T
Hamaguchi
Michinari
M
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D006657:Histones; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D012694:Serine; D051231:Farnesyltranstransferase; D015688:Oncogene Protein pp60(v-src); D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D018631:ras Proteins; C054474:manumycin