Research Center for Medical Genetics RAMS, Moscow, Russian Federation, Russia.
Bioessays. 2013 Jul;35(7):586-96. doi: 10.1002/bies.201300002. Epub 2013 Apr 17.
The KCTD family includes tetramerization (T1) domain containing proteins with diverse biological effects. We identified a novel member of the KCTD family, BTBD10. A comprehensive analysis of protein-protein interactions (PPIs) allowed us to put forth a number of testable hypotheses concerning the biological functions for individual KCTD proteins. In particular, we predict that KCTD20 participates in the AKT-mTOR-p70 S6k signaling cascade, KCTD5 plays a role in cytokinesis in a NEK6 and ch-TOG-dependent manner, KCTD10 regulates the RhoA/RhoB pathway. Developmental regulator KCTD15 represses AP-2α and contributes to energy homeostasis by suppressing early adipogenesis. TNFAIP1-like KCTD proteins may participate in post-replication DNA repair through PCNA ubiquitination. KCTD12 may suppress the proliferation of gastrointestinal cells through interference with GABAb signaling. KCTD9 deserves experimental attention as the only eukaryotic protein with a DNA-like pentapeptide repeat domain. The value of manual curation of PPIs and analysis of existing high-throughput data should not be underestimated.
KCTD 家族包括具有多种生物学效应的四聚化 (T1) 结构域蛋白。我们鉴定了 KCTD 家族的一个新成员 BTBD10。对蛋白质-蛋白质相互作用 (PPI) 的全面分析使我们能够提出许多关于单个 KCTD 蛋白生物学功能的可测试假设。特别是,我们预测 KCTD20 参与 AKT-mTOR-p70 S6k 信号级联,KCTD5 以 NEK6 和 ch-TOG 依赖性方式在胞质分裂中发挥作用,KCTD10 调节 RhoA/RhoB 途径。发育调节剂 KCTD15 通过抑制早期脂肪生成来抑制 AP-2α 并有助于能量稳态。TNFAIP1 样 KCTD 蛋白可能通过 PCNA 泛素化参与复制后 DNA 修复。KCTD12 可能通过干扰 GABAb 信号来抑制胃肠道细胞的增殖。KCTD9 值得进行实验研究,因为它是唯一具有 DNA 样五肽重复结构域的真核蛋白。人工整理 PPI 和分析现有高通量数据的价值不应被低估。