Entamoeba histolytica sirtuin EhSir2a deacetylates tubulin and regulates the number of microtubular assemblies during the cell cycle.
Entamoeba histolytica sirtuin EhSir2a deacetylates tubulin and regulates the number of microtubular assemblies during the cell cycle.
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DOI：
10.1111/j.1462-5822.2010.01449.x
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发表时间：
2010-07
影响因子：
3.4
通讯作者：
Lohia A
中科院分区：
文献类型：
--
作者：
Dam S;Lohia A
我们在溶组织内阿米巴中发现了四个sirtuin基因，其中两个与真核sirtuins相似，两个与细菌和古菌sirtuins相似。真核 Sirtuin 同源物 EhSir2a 显示 NAD+ 依赖性脱乙酰酶活性，并且对 III 类 HDAC 抑制剂敏感。 EhSir2a 在不同细胞位点的定位表明这种脱乙酰酶可能有多个靶标。在酵母双杂交遗传筛选中使用溶组织内阿米巴 cDNA 文库，我们鉴定了几种与 EhSir2a 结合的蛋白质。这些蛋白质包括 Eh α-微管蛋白，其与 EhSir2a 的相互作用在溶组织内阿米巴中得到了验证。我们已经证明，EhSir2a 使微管蛋白脱乙酰化，并与溶组织内阿米巴中的微管一起定位。稳定转化体中 EhSir2a 表达水平的增加导致血清同步化细胞中微管组件数量减少。这种效应被 EhSir2a 脱乙酰酶结构域的突变所消除，表明 EhSir2a 脱乙酰酶活性影响溶组织内阿米巴细胞周期期间微管组件的稳定性和数量。我们的结果表明，EhSir2a 对微管蛋白的表观遗传修饰是调节溶组织内阿米巴微管组装的机制之一。
We have discovered four sirtuin genes in Entamoeba histolytica, two of which are similar to eukaryotic sirtuins and two to bacterial and archaeal sirtuins. The eukaryotic sirtuin homolog, EhSir2a showed NAD+ dependent deacetylase activity and was sensitive to Class III HDAC inhibitors. Localization of EhSir2a at different cellular sites suggested that this deacetylase could have multiple targets. Using an E. histolytica cDNA library in the yeast two-hybrid genetic screen, we identified several proteins that bound to EhSir2a. These proteins included Eh α-tubulin, whose interaction with EhSir2a was validated in E. histolytica. We have shown that EhSir2a deacetylated tubulin and localised with microtubules in E. histolytica. Increased expression levels of EhSir2a in stable transformants led to reduced number of microtubular assemblies in serum synchronised cells. This effect was abrogated by mutations in the deacetylase domain of EhSir2a, showing that EhSir2a deacetylase activity affected the stability and number of microtubular assemblies during the cell cycle of E. histolytica. Our results suggest that epigenetic modification of tubulin by EhSir2a is one of the mechanisms that regulates microtubular assembly in E. histolytica.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
3.8
作者：
Mukherjee C;Majumder S;Lohia A
通讯作者：
Lohia A
影响因子：
3.1
作者：
MacFarlane, RC;Singh, U
通讯作者：
Singh, U
影响因子：
3.9
作者：
HAMEL, E;LIN, CM
通讯作者：
LIN, CM
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA