論文 - 丹下　正一朗

Roles of histone methyl-modifying enzymes in development and progression of cancer

Takeshi Suzuki, Minoru Terashima, Shoichiro Tange, Akihiko Ishimura

Cancer Science ( Wiley )  104 ( 7 ) 795 - 800  2013年05月

DOI

Initiation of human astrovirus type 1 infection was blocked by inhibitors of phosphoinositide 3-kinase

Shoichiro Tange, Yan Zhou, Yuko Nagakui-Noguchi, Takeshi Imai, Akira Nakanishi

VIROLOGY JOURNAL ( BIOMED CENTRAL LTD )  10   153  2013年05月  [査読有り]

　概要を見る

Background: Upon initial contact with a virus, host cells activate a series of cellular signaling cascades that facilitate viral entry and viral propagation within the cell. Little is known about how the human astrovirus (HAstV) exploits signaling cascades to establish an infection in host cells. Recent studies showed that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is important for HAstV infection, though the involvement of other signaling cascades remains unclear. Methods: A panel of kinase blockers was used to search for cellular signaling pathways important for HAstV1 infection. To determine their impact on the infectious process, we examined viral gene expression, RNA replication, and viral RNA and capsid protein release from host cells. Results: Inhibitors of phosphoinositide 3-kinase (PI3K) activation interfered with the infection, independent of their effect on ERK 1/2 activation. Activation of the PI3K signaling cascade occurred at an early phase of the infection, judging from the timeframe of Akt phosphorylation. PI3K inhibition at early times, but not at later times, blocked viral gene expression. However, inhibiting the downstream targets of PI3K activation, Akt and Rac1, did not block infection. Inhibition of protein kinase A (PKA) activation was found to block a later phase of HAstV1 production. Conclusions: Our results reveal a previously unknown, essential role of PI3K in the life cycle of HAstV1. PI3K participates in the early stage of infection, possibly during the viral entry process. Our results also reveal the role of PKA in viral production.

DOI PubMed

An SV40 mutant defective in VP4 expression exhibits a temperature-sensitive growth defect

Shoichiro Tange, Takeshi Imai, Akira Nakanishi

VIRUS RESEARCH ( ELSEVIER SCIENCE BV )  157 ( 1 ) 116 - 120  2011年04月  [査読有り]

　概要を見る

On reexamination of temperature-sensitive D-type (tsD) mutants of simian virus 40 (SV40), we found that the tsD222 mutant is identical to the VP2 M228I mutant, which is defective in VP4 expression, at the nucleotide level. Although a previous study reported that lack of VP4 caused defects in viral dissemination in BSC-1 cells, this mutant showed a temperature-sensitive growth defect in CV-1 cells. tsD101:VP3 Q113K and tsD202:VP3 P108S exhibited a growth phenotype similar to that of tsD222, and they retained the VP4 open reading frame (ORF). These three mutants did not complement each other, suggesting that their defects were functionally indistinguishable. Transduction of the SV40 vector expressing wild-type VP4 in tsD222-infected cells did not ameliorate the growth defect at the non-permissive temperature. The results indicate that tsD mutation in minor capsid proteins has a more profound impact on viral propagation, and that lack of VP4 ORF seems to have little influence on viral growth. (C) 2011 Elsevier B.V. All rights reserved.

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Phosphorylation of histone H3 at Ser10: Its role in cell transformation by v-Src

Shoichiro Tange, Satoko Ito, Takeshi Senga, Michinari Hamaguchi

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE )  386 ( 4 ) 588 - 592  2009年09月  [査読有り]

　概要を見る

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. (C) 2009 Elsevier Inc. All rights reserved.

DOI PubMed