The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer.
The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer.
复制标题
DTX蛋白家族：癌症中新兴的E3泛素连接酶。
DOI：
10.3390/cells12131680
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发表时间：
2023-06-21
期刊：
影响因子：
6
通讯作者：
Carnevale, Vincenzo
中科院分区：
文献类型：
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作者：
Scalia, Pierluigi;Williams, Stephen J.;Suma, Antonio;Carnevale, Vincenzo
关键词：
直到最近，Deltex（DTX）蛋白一直被认为是推定的E3连接酶，这是基于其蛋白编码序列中存在E3 RING结构域。人DTX家族包括DTX 1、DTX 2、DTX 3、DTX 3L和DTX 4。尽管我们对这类E3-泛素连接酶的了解仍处于早期阶段，但我们对它们在肿瘤发生中的作用的理解正在开始展开。事实上，最近发表的研究使我们能够定义特定的生物情景，并进一步巩固基于证据的工作假设。根据目前的证据，所有DTX家族成员都参与Notch信号传导的调节，表明在该途径的调节中具有遗传上保守的作用。事实上，更多的证据揭示了这些蛋白质在其他信号复合物和癌症促进机制中的广泛参与，而不仅仅是NOTCH信号。具体而言，已知DTX 3表达两种同种型变体（DTX 3a和DTX 3b）。最近对癌症中第三种同种型变体（DTX 3c）的鉴定和克隆，及其在癌细胞中EphB 4降解中的特异性参与，进一步阐明了这组蛋白质及其在癌症中的特定作用。在此，我们回顾了E3泛素连接酶家族的累积知识，特别关注DTX亚型的潜在致癌作用，并根据有关该蛋白家族的细胞靶点和调节信号通路的快速扩展的发现。此外，使用比较和生物信息学的方法，我们在这里公开了一个新的推定的基序，这可能有助于了解这些蛋白质的成员之间的生物学和上下文的差异，这个家庭的成员。
Until recently, Deltex (DTX) proteins have been considered putative E3 ligases, based on the presence of an E3 RING domain in their protein coding sequence. The human DTX family includes DTX1, DTX2, DTX3, DTX3L and DTX4. Despite the fact that our knowledge of this class of E3-ubiquitin ligases is still at an early stage, our understanding of their role in oncogenesis is beginning to unfold. In fact, recently published studies allow us to define specific biological scenarios and further consolidate evidence-based working hypotheses. According to the current evidence, all DTX family members are involved in the regulation of Notch signaling, suggesting a phylogenetically conserved role in the regulation of this pathway. Indeed, additional evidence reveals a wider involvement of these proteins in other signaling complexes and cancer-promoting mechanisms beyond NOTCH signaling. DTX3, in particular, had been known to express two isoform variants (DTX3a and DTX3b). The recent identification and cloning of a third isoform variant in cancer (DTX3c), and its specific involvement in EphB4 degradation in cancer cells, sheds further light on this group of proteins and their specific role in cancer. Herein, we review the cumulative knowledge of this family of E3 Ubiquitin ligases with a specific focus on the potential oncogenic role of DTX isoforms in light of the rapidly expanding findings regarding this protein family’s cellular targets and regulated signaling pathways. Furthermore, using a comparative and bioinformatic approach, we here disclose a new putative motif of a member of this family which may help in understanding the biological and contextual differences between the members of these proteins.
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影响因子：
4.1
作者：
Wu, Yi-Lin;Pan, Le-Han;Yi, Zhu-Jun;Zhang, Wen-Feng;Gong, Jian-Ping
通讯作者：
Gong, Jian-Ping
影响因子：
5.6
作者：
Hu, Wei;Hu, Yaorui;Pei, Yao;Li, Rongrong;Xu, Fuyi;Chi, Xiaodong;Mi, Jia;Bergquist, Jonas;Lu, Lu;Zhang, Luping;Yang, Chunhua
通讯作者：
Yang, Chunhua
影响因子：
5.7
作者：
Che, Karlhans Fru;Shankar, Esaki Muthu;Larsson, Marie
通讯作者：
Larsson, Marie
影响因子：
32.4
作者：
Hsiao, Huey-Wen;Liu, Wen-Hsien;Lai, Ming-Zong
通讯作者：
Lai, Ming-Zong
NLRP4 通过泛素连接酶 DTX4 靶向激酶 TBK1 进行降解，从而负调节 I 型干扰素信号传导
影响因子：
30.5
作者：
通讯作者：
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