Ubiquitin-proteasome-dependent degradation of TBP-like protein is prevented by direct binding of TFIIA
Ubiquitin-proteasome-dependent degradation of TBP-like protein is prevented by direct binding of TFIIA
复制标题
TFIIA 的直接结合可防止 TBP 样蛋白的泛素蛋白酶体依赖性降解
DOI：
10.1111/gtc.12441
复制
发表时间：
2016
期刊：
影响因子：
2.1
通讯作者：
Tamura T.
中科院分区：
文献类型：
--
作者：
Isogai M;Suzuki H;Maeda R;Tamura T.
虽然大多数基因表达是由基于TATA结合蛋白（TBP）的转录机制驱动的，但据报道，TBP相关因子（TRFs）也参与了基因表达的调控。TBP样蛋白（TLP）是TRFs中与TFIIA亲和力最高的蛋白质之一，最近被证明在基因调控中具有重要作用。然而，TLP的水平如何在体内被调节仍然是未知的。本研究探讨了TLP蛋白在体内的翻转机制以及维持TLP蛋白量的因素。我们发现，TLP被泛素-蛋白酶体系统快速降解，与TFIIA的紧密相互作用导致TLP免受泛素-蛋白酶体依赖性降解。TLP的半衰期不到几个小时，蛋白酶体抑制剂MG 132特异性抑制TLP降解。此外，敲低和过表达实验表明，TFIIA参与TLPin的体内稳定。因此，我们发现了TLP的一个新特性，即与TFIIA的相互作用对于抑制TLP的蛋白酶体依赖性周转至关重要，从而进一步了解了TLP控制的基因调控。
Although the majority of gene expression is driven by TATA‐binding protein (TBP)‐based transcription machinery, it has been reported that TBP‐related factors (TRFs) are also involved in the regulation of gene expression. TBP‐like protein (TLP), which is one of the TRFs and exhibits the highest affinity to TFIIA among known proteins, has recently been showed to have significant roles in gene regulation. However, how the level of TLP is maintainedin vivohas remained unknown. In this study, we explored the mechanism by which TLP protein is turned overin vivoand the factor that maintains the amount of TLP. We showed that TLP is rapidly degraded by the ubiquitin‐proteasome system and that tight interaction with TFIIA results in protection of TLP from ubiquitin‐proteasome‐dependent degradation. The half‐life of TLP was shown to be less than a few hours, and the proteasome inhibitor MG132 specifically suppressed TLP degradation. Moreover, knockdown and over‐expression experiments showed that TFIIA is engaged in stabilization of TLPin vivo. Thus, we showed a novel characteristic of TLP, that is, interaction with TFIIA is essential to suppress proteasome‐dependent turnover of TLP, providing a further insight into TLP‐governed gene regulation.