Sumoylation of transcription factor Tec1 regulates signaling of mitogen-activated protein kinase pathways in yeast.

Sumoylation of transcription factor Tec1 regulates signaling of mitogen-activated protein kinase pathways in yeast.
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DOI:
10.1371/journal.pone.0007456
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发表时间:
2009-10-14
期刊:
影响因子:
3.7
通讯作者:
Suntay K
Suntay K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Y;Abu Irqeba A;Ayalew M;Suntay K

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Tec1是酵母有丝分裂原激活蛋白激酶(MAPK)途径中的一个转录因子,控制着侵袭性生长。在此之前,我们曾报道,在正常生长的细胞中,Tec1蛋白的一部分在残基赖氨酸54上发生总甲基化。在这里,我们描述了Tec1总甲基化的调节和功能后果。我们发现,直接激活Tec1的MAPK Kss1的激活导致Tec1总甲基化的减少和Tec1转录活性的同时增加。与总甲基化在抑制Tec1活性中的作用一致,特别是通过将Tec1与总甲基化酶Ubc9融合来增加Tec1的总甲基化,导致Tec1转录活性的急剧下降。侵入性增长在Tec1-Ubc9中也受到了影响。相反,将苏莫化位点突变体Tec1,即Tec1K54R融合到Ubc9上并没有显著改变转录激活,对侵袭性生长的影响较小。综上所述,这些发现证明了调控的总和甲基化是调节Tec1活性的一种机制,并验证了Ubc9融合指导的总总甲基化是研究蛋白质总总甲基化的有用方法。
Tec1 is a transcription factor in the yeast mitogen-activated protein kinase (MAPK) pathway that controls invasive growth. Previously we reported that a fraction of Tec1 protein is sumoylated on residue lysine 54 in normally growing cells. Here we describe regulation and functional consequences of Tec1 sumoylation. We found that activation of Kss1, the MAPK that directly activates Tec1, results in a decrease in Tec1 sumoylation and a concurrent increase of Tec1 transcriptional activity. Consistent with a role of sumoylation in inhibiting Tec1 activity, specifically increasing sumoylation of Tec1 by fusing it to the sumoylating enzyme Ubc9 leads to a dramatic decrease of Tec1 transcriptional activity. Invasive growth is also compromised in Tec1-Ubc9. In contrast, fusing sumoylation-site mutant Tec1, i.e., Tec1K54R, to Ubc9 did not significantly alter transcriptional activation and had a less effect on invasive growth. Taken together, these findings provide evidence for regulated sumoylation as a mechanism to modulate the activity of Tec1 and validate Ubc9 fusion-directed sumoylation as a useful approach for studying protein sumoylation.
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