A mechanism for inhibiting the SUMO pathway
A mechanism for inhibiting the SUMO pathway
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DOI：
10.1016/j.molcel.2004.11.007
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发表时间：
2004-11-19
期刊：
影响因子：
16
通讯作者：
Chiocca, S
中科院分区：
文献类型：
--
作者：
Boggio, R;Colombo, R;Chiocca, S
SUMO途径平行于经典的泛素化途径，具有三个独立的步骤：涉及酶E1的活化，涉及E2酶UBC 9的缀合，以及通过UBC 9和E3连接酶的协同缔合的底物修饰。我们在这里报告，腺病毒蛋白Gam 1抑制SUMO通路通过干扰E1的活性（SAE 1/SAE 2）。在体内，Gam 1表达导致SAE 1/SAE 2失活，SAE 1/SAE 2和UBC 9消失，以及蛋白类小泛素化的总体抑制。这导致一些启动子的转录激活，并且与所涉及的转录激活因子的类小泛素化的抑制直接相关。我们的研究结果确定了一种干扰SUMO通路和转录的机制，这可能对新型药物的设计产生影响。他们还再次指出了真核病毒通过靶向基本的生物化学过程来干扰宿主细胞生物学的非凡能力。
The SUMO pathway parallels the classical ubiquitinylation pathway with three discrete steps: activation involving the enzyme E1, conjugation involving the E2 enzyme UBC9, and substrate modification through the cooperative association of UBC9 and E3 ligases. We report here that the adenoviral protein Gam1 inhibits the SUMO pathway by interfering with the activity of E1 (SAE1/SAE2). In vivo, Gam1 expression leads to SAE1/SAE2 inactivation, both SAE1/SAE2 and UBC9 disappearance, and overall inhibition of protein sumoylation. This results in transcriptional activation of some promoters and is directly linked to inhibition of sumoylation of the transcriptional activators involved. Our results identify a mechanism for interfering with the SUMO pathway and with transcription that could have an impact in the design of novel pharmaceutical agents. They also point out once again to the extraordinary ability of eukaryotic viruses to interfere with the biology of host cells by targeting fundamental biochemical processes.