Tribbles-Related Protein Family Members as Regulators or Substrates of the Ubiquitin-Proteasome System in Cancer Development.
Tribbles-Related Protein Family Members as Regulators or Substrates of the Ubiquitin-Proteasome System in Cancer Development.
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DOI：
10.2174/1568009616666151112122645
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发表时间：
2016-01
影响因子：
3
通讯作者：
Satoshi Sakai;Chiharu Miyajima;C. Uchida;Yuka Itoh;H. Hayashi;Yasumichi Inoue
中科院分区：
文献类型：
--
作者：
Satoshi Sakai;Chiharu Miyajima;C. Uchida;Yuka Itoh;H. Hayashi;Yasumichi Inoue
摩擦相关蛋白（TRB）家族成员是果蝇摩擦相关蛋白（Drosophila tribbles）的哺乳动物直系同源物。Tribbles最初被鉴定为果蝇发育过程中的细胞周期调节剂。Tribbles基因在进化上是保守的，在哺乳动物中已发现三个TRB基因（TRB 1、TRB 2和TRB 3）。TRB被认为是假激酶，因为它们缺乏ATP结合位点或激酶活性所必需的保守催化基序之一。相反，TRB在各种细胞过程中发挥重要作用，作为支架或衔接子，以促进靶蛋白的降解和调节几个关键的信号通路。最近的研究集中在TRB在肿瘤发生和肿瘤进展中的作用。本文就TRB家族成员通过调节泛素-蛋白酶体系统在肿瘤发生中的生理作用进行综述，并探讨TRB作为肿瘤生物标志物或潜在治疗靶点的可能性。
Tribbles-related protein (TRB) family members are the mammalian orthologs of Drosophila tribbles. Tribbles was originally identified as a cell cycle regulator during Drosophila development. Tribbles genes are evolutionary conserved, and three TRB genes (TRB1, TRB2 and TRB3) have been identified in mammals. TRBs are considered pseudokinases because they lack an ATP binding site or one of the conserved catalytic motifs essential for kinase activity. Instead, TRBs play important roles in various cellular processes as scaffolds or adaptors to promote the degradation of target proteins and to regulate several key signaling pathways. Recent research has focused on the role of TRBs in tumorigenesis and neoplastic progression. In this review, we focus on the physiological roles of TRB family members in tumorigenesis through the regulation of the ubiquitin-proteasome system and discuss TRBs as biomarkers or potential therapeutic targets in cancer.