The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting Chlamydia effectors from degradation.
The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting Chlamydia effectors from degradation.
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Cdu1 的乙酰化酶活性通过保护衣原体效应子免遭降解来调节细菌从受感染细胞中排出。
DOI：
10.1101/2023.02.28.530337
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Valdivia,RaphaelH
中科院分区：
文献类型：
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作者：
Bastidas,RobertJ;Kędzior,Mateusz;Davidson,RobertK;Walsh,StephenC;Dolat,Lee;Sixt,BarbaraS;Pruneda,JonathanN;Coers,Jörn;Valdivia,RaphaelH
许多细胞过程是由泛素介导的蛋白酶体降解调节的。病原体可以通过递送具有去泛素化（DUB）活性的蛋白质来调节真核生物的蛋白质水解。专性细胞内病原体沙眼衣原体分泌Cdu 1（ChlaDUB1），一种双重去泛素化酶和赖氨酸乙酰转移酶，可能通过调节宿主和细菌蛋白的泛素化来促进高尔基体重塑和受感染宿主细胞的存活。在这里，我们确定了Cdu1的乙酰化酶，而不是它的DUB活性是重要的，以保护Cdu1从泛素介导的降解。我们进一步确定了三个C。沙眼衣原体蛋白在含有病原体的空泡（InaC，IpaM，和CTL 0480），需要Cdu 1的乙酰化酶活性的保护降解，并确定Cdu 1和这些Cdu 1保护的蛋白质是所需的衣原体从宿主细胞的最佳出口。这些发现突出了病原体介导的保护毒力因子在其递送到宿主细胞后免于降解的非经典机制以及分泌的效应蛋白的协调调节。
Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Chlamydia trachomatis secretes Cdu1 (ChlaDUB1), a dual deubiquitinase and Lys-acetyltransferase, that promotes Golgi remodeling and survival of infected host cells presumably by regulating the ubiquitination of host and bacterial proteins. Here, we determined that Cdu1’s acetylase but not its DUB activity is important to protect Cdu1 from ubiquitin-mediated degradation. We further identified three C. trachomatis proteins on the pathogen-containing vacuole (InaC, IpaM, and CTL0480) that required Cdu1‘s acetylase activity for protection from degradation and determined that Cdu1 and these Cdu1-protected proteins are required for optimal egress of Chlamydia from host cells. These findings highlight a non-canonical mechanism of pathogen-mediated protection of virulence factors from degradation after their delivery into host cells and the coordinated regulation of secreted effector proteins.