Functional importance of the DNA binding activity of Candida albicans Czf1p.

Functional importance of the DNA binding activity of Candida albicans Czf1p.
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DOI:
10.1371/journal.pone.0039624
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kumamoto CA
Kumamoto CA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Petrovska I;Kumamoto CA

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人类机会致病菌白色念珠菌在各种信号的作用下,在酵母和菌丝状态之间发生可逆的形态学转变。一种这样的环境触发因素是在半固体基质如琼脂培养基内生长。这种生长条件是令人感兴趣的,因为它可以模拟C.在感染过程中与宿主组织接触的白色念珠菌。在半固体基质内生长期间,菌丝生长受到转录调节因子Czf1p的正调控,受到第二关键转录调节因子Efg1p的负调控。遗传学研究表明,Czf1p,转录调节因子的锌簇家族的成员,发挥其功能,反对Efg1p对基质诱导的丝状生长的抑制作用。我们研究了Czf1p的两种已知活性的重要性,DNA结合和与Efg1p的相互作用。我们发现,这两个活动是可分离的突变,使我们能够证明,Czf1p的DNA结合活性是必不可少的,其作为一个积极的调节器的形态发生的作用。然而,令人惊讶的是,与Efg1p的相互作用似乎在很大程度上是不稳定的。我们的研究提供了第一个证据的DNA结合活性的Czf1p在形态酵母菌丝过渡触发矩阵嵌入式增长的关键作用。
The human opportunistic pathogen Candida albicans undergoes a reversible morphological transition between the yeast and hyphal states in response to a variety of signals. One such environmental trigger is growth within a semisolid matrix such as agar medium. This growth condition is of interest because it may mimic the growth of C. albicans in contact with host tissue during infection. During growth within a semisolid matrix, hyphal growth is positively regulated by the transcriptional regulator Czf1p and negatively by a second key transcriptional regulator, Efg1p. Genetic studies indicate that Czf1p, a member of the zinc-cluster family of transcriptional regulators, exerts its function by opposing the inhibitory influence of Efg1p on matrix-induced filamentous growth. We examined the importance of the two known activities of Czf1p, DNA-binding and interaction with Efg1p. We found that the two activities were separable by mutation allowing us to demonstrate that the DNA-binding activity of Czf1p was essential for its role as a positive regulator of morphogenesis. Surprisingly, however, interactions with Efg1p appeared to be largely dispensable. Our studies provide the first evidence of a key role for the DNA-binding activity of Czf1p in the morphological yeast-to-hyphal transition triggered by matrix-embedded growth.
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