Cloning and Characterization of DULP, a Novel Ubiquitin-Like Molecule from Human Dendritic Cells

Cloning and Characterization of DULP, a Novel Ubiquitin-Like Molecule from Human Dendritic Cells
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DULP(一种来自人类树突状细胞的新型泛素样分子)的克隆和表征

DOI:
10.1038/cmi.2009.4
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发表时间:
2009-02-01
影响因子:
24.1
通讯作者:
Yu, Yizhi
Yu, Yizhi
中科院分区:
医学1区
文献类型:
--
作者:
Liu, Guoyan;Liu, Shuxun;Yu, Yizhi

文献摘要

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我们从人树突状细胞中鉴定了一种新的泛素样分子DULP。DULP含有一个与泛素具有26%同一性和34%相似性的结构域,并且它具有相应的Ile-44疏水补丁,所述Ile-44疏水补丁被单-或多-泛素用于与泛素相互作用基序(UIM)或泛素相关结构域(乌巴)相互作用。泛素同源结构域中对应于泛素6位的赖氨酸残基也是保守的,其参与形成可结合蛋白酶体亚基Rpn 10/S5 a的多泛素链。然而,DULP不具有泛素缀合所需的高度保守的C-末端Gly-Gly或形成多聚泛素链以靶底物降解所需的Lys-48,这表明它可能是一种新的泛素结构域蛋白(UDP)。DULP在许多细胞中广泛表达,并且泛素同源结构域不被切割。我们还证实DULP表达在细胞核中富集,而在细胞质中弱得多。此外,我们发现DULP在293 T细胞中过表达可诱导细胞凋亡,这可能与线粒体或蛋白酶体途径无关,具体机制尚不清楚。需要进一步的研究来确定DULP的确切生物学功能。细胞与分子免疫学2009;6(1):27-33.
We identified a novel ubiquitin-like molecule DULP from human dendritic cells. DULP contains a domain that shares 26% identity and 34% similarity with ubiquitin, and it possesses the corresponding Ile-44 hydrophobic patch used by mono- or poly-ubiquitin to interact with a ubiquitin-interaction motif (UIM) or ubiquitin-associated domain (UBA). Lysine residue corresponding to 6 of ubiquitin, which is involved in the formation of a multi-ubiquitin chain that can bind proteasomal subunit Rpn10/S5a, is also conserved in its ubiquitin-homology domain. However, DULP does not possess the highly conserved C-terminus Gly-Gly required for ubiquitin conjugation or the Lys-48 required for the formation of polyubiquitin chain to target substrates for degradation, suggesting it might be a novel ubiquitin-domain protein (UDP). DULP was found widely expressed in many cells and the ubiquitin-homology domain was not cleaved. We also confirmed that DULP expression was enriched in the nucleus and much weaker in the cytosol. Besides, we found that overexpression of DULP in 293T cells induced apoptosis, which might not be associated with the mitochondrial or proteasome pathway, with the specific mechanism remain unclear. Further investigations are needed to identify the precise biological functions of DULP. Cellular & Molecular Immunology. 2009;6(1):27-33.