DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways
DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways
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DOI：
10.1186/1472-6807-6-1
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发表时间：
2006-01-05
影响因子：
--
通讯作者：
Rees, DJG
中科院分区：
文献类型：
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作者：
Pugh, DJR;Ab, E;Rees, DJG
背景：RBBP 6是一种250 kDa的剪接相关蛋白，由于存在RING指结构域，已被鉴定为E3连接酶。在人类和小鼠中，它与p53和Rb相互作用，并在诱导细胞凋亡和调节细胞周期中发挥作用。RBBP 6最近已被证明是高度上调，在食管癌，是一个有前途的目标，免疫治疗对diseases.Results：我们在这里显示，使用heteropedNMR的RBBP 6的N-末端81个氨基酸构成一个新的泛素样结构域，我们称之为DWNN结构域。该结构域缺乏K-48和K-63的保守等价物，尽管K-6和K-29的等价物是高度保守的，尽管不是绝对保守的。作为参与泛素化的蛋白质的特征的双甘氨酸基序在人类和小鼠的结构域中发现，尽管它并不存在于所有生物体中。它形成RBBP 6的三结构域形式的一部分，所述RBBP 6包含DWNN结构域、锌关节和RING指结构域，所述RBBP 6在迄今为止检查的所有真核生物基因组中发现，在大多数情况下以单拷贝数存在。结论：DWNN是一个新的泛素样结构域，仅存在于RBBP 6剪接相关蛋白家族的N端。该结构域的泛素样结构大大增加了RBBP 6通过某种形式的泛素样修饰发挥功能的可能性。此外，DWNN结构域在高等脊椎动物中独立表达的事实使我们提出该结构域本身可能作为其他蛋白质的新型泛素样修饰剂发挥作用。
Background: RBBP6 is a 250 kDa splicing-associated protein that has been identified as an E3 ligase due to the presence of a RING finger domain. In humans and mice it interacts with both p53 and Rb, and plays a role in the induction of apoptosis and regulation of the cell cycle. RBBP6 has recently been shown to be highly up-regulated in oesophageal cancer, and to be a promising target for immunotherapy against the disease.Results: We show here using heteronuclear NMR that the N-terminal 81 amino acids of RBBP6 constitute a novel ubiquitin-like domain, which we have called the DWNN domain. The domain lacks conserved equivalents of K-48 and K-63, although the equivalents of K-6 and K-29 are highly, although not absolutely, conserved. The di-glycine motif that is characteristic of proteins involved in ubiquitination is found in the human and mouse form of the domain, although it is not present in all organisms. It forms part of a three-domain form of RBBP6 containing the DWNN domain, a zinc knuckle and a RING finger domain, which is found in all eukaryotic genomes so far examined, in the majority of cases at single copy number. The domain is also independently expressed in vertebrates as a single domain protein.Conclusion: DWNN is a novel ubiquitin-like domain found only at the N-terminus of the RBBP6 family of splicing-associated proteins. The ubiquitin-like structure of the domain greatly increases the likelihood that RBBP6 functions through some form of ubiquitin-like modification. Furthermore, the fact that the DWNN domain is independently expressed in higher vertebrates leads us to propose that the domain may itself function as a novel ubiquitin-like modifier of other proteins.