TY  - JOUR
A1  - Fischer, Annette
A1  - Harrison, Kelly S
A1  - Ramirez, Yesid
A1  - Auer, Daniela
A1  - Chowdhury, Suvagata Roy
A1  - Prusty, Bhupesh K
A1  - Sauer, Florian
A1  - Dimond, Zoe
A1  - Kisker, Caroline
A1  - Hefty, P Scott
A1  - Rudel, Thomas
T1  - Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense
JF  - eLife
N2  - Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique α-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl-1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFNγ and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a deubiquitinating activity exerting a function in selective stabilization of host proteins and protection from host defense.
KW  - cell-autonomous defense
KW  - Chlamydia trachomatis
KW  - deubiquitinase
KW  - Mcl-1
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171073
VL  - 6
IS  - e21465
ER  -