Genome-wide screening for genes associated with valproic acid sensitivity in fission yeast.
Genome-wide screening for genes associated with valproic acid sensitivity in fission yeast.
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DOI：
10.1371/journal.pone.0068738
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Zhang L;Ma N;Liu Q;Ma Y
我们一直在研究丙戊酸（VPA）在分裂酵母裂糖酵母（Schizosaccharomyces pombe）中的作用机制，通过开发对VPA过敏的突变体的遗传筛选。在本研究中，我们对3004株单倍体缺失菌株进行了全基因组筛选，确认148株缺失菌株对VPA敏感。在148株菌株中，93株菌株对另一种脂肪酸HDAC抑制剂丁酸钠（SB）也有敏感性，55株菌株对VPA敏感，但对SB不敏感。有趣的是，我们发现VPA和SB处理均能显著提高野生型细胞中Atf1的转录活性。然而，在编码I类HDAC的突变等位基因clr6-1中，VPA-和SB都没有诱导Atf1转录活性的激活。我们还发现VPA而不是SB引起细胞质Ca2+水平升高。我们进一步发现细胞质Ca2+的增加是由于Ca2+通过Cch1-Yam8通道复合物从细胞外介质流入引起的。总之，我们目前的研究表明VPA和SB在裂变酵母的多个生理过程中发挥着相似但不同的作用。
We have been studying the action mechanisms of valproic acid (VPA) in fission yeast Schizosaccharomyces pombe by developing a genetic screen for mutants that show hypersensitivity to VPA. In the present study, we performed a genome-wide screen of 3004 haploid deletion strains and confirmed 148 deletion strains to be VPA sensitive. Of the 148 strains, 93 strains also showed sensitivity to another aliphatic acids HDAC inhibitor, sodium butyrate (SB), and 55 strains showed sensitivity to VPA but not to SB. Interestingly, we found that both VPA and SB treatment induced a marked increase in the transcription activity of Atf1 in wild-type cells. However, in clr6-1, a mutant allele the clr6+ gene encoding class I HDAC, neither VPA- nor SB induced the activation of Atf1 transcription activity. We also found that VPA, but not SB, caused an increase in cytoplasmic Ca2+ level. We further found that the cytoplasmic Ca2+ increase was caused by Ca2+ influx from extracellular medium via Cch1-Yam8 channel complex. Altogether, our present study indicates that VPA and SB play similar but distinct roles in multiple physiological processes in fission yeast.
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影响因子：
3.7
作者：
Calvo IA;Gabrielli N;Iglesias-Baena I;García-Santamarina S;Hoe KL;Kim DU;Sansó M;Zuin A;Pérez P;Ayté J;Hidalgo E
通讯作者：
Hidalgo E
影响因子：
4.8
作者：
Hirayama, S;Sugiura, R;Kuno, T
通讯作者：
Kuno, T
影响因子：
3.8
作者：
Kennedy, Patrick J.;Vashisht, Ajay A.;Russell, Paul
通讯作者：
Russell, Paul
影响因子：
2.9
作者：
FRANCESCHETTI, S;HAMON, B;HEINEMANN, U
通讯作者：
HEINEMANN, U
影响因子：
3.7
作者：
Kita A;Li C;Yu Y;Umeda N;Doi A;Yasuda M;Ishiwata S;Taga A;Horiuchi Y;Sugiura R
通讯作者：
Sugiura R