Sde Proteins Coordinate Ubiquitin Utilization and Phosphoribosylation to Establish and Maintain theLegionellaReplication Vacuole DOI Creative Commons

Kristin M. Kotewicz,

Mengyun Zhang, Seongok Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 7, 2023

Abstract The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification Reticulon 4 (Rtn4). have two additional activities unclear relevance the infection process: K63 linkage-specific deubiquitination and phosphoribosyl polyubiquitin (pR-Ub). We show here activity (DUB) stimulates ER while pR-Ub protects replication vacuole from cytosolic surveillance by autophagy. Loss DUB is lowered Rtn4, consistent with fueling production pR-Ub-Rtn4. In parallel, polyUb, in a region protein known as isoleucine patch, prevents binding autophagy adapter p62. An inability mutants modify polyUb results immediate p62 association, critical precursor autophagic attack. ability WT block association decays quickly after bacterial infection, predicted presence previously characterized L. effectors inactivate remove polyUb. sum, these accessory act stimulate protect innate immune sensing temporal fashion.

Язык: Английский

Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition DOI Creative Commons
Min Wan, Marena E. Minelli, Qiuye Zhao

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 30, 2024

Ubiquitination is a posttranslational modification in eukaryotes that plays significant role the infection of intracellular microbial pathogens, such as Legionella pneumophila. While Legionella-containing vacuole (LCV) coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. Here, we report Sdc and Sde families effectors work together to build ubiquitinated species around LCV. The catalyze canonical polyubiquitination directly on host targets or phosphoribosyl-Ub conjugated Sde. Remarkably, Ub moieties within poly-Ub chains are either modified phosphoribosyl group PDE domain-containing covalently attached other substrates via Sde-mediated phosphoribosyl-ubiquitination. Furthermore, these modifications prevent adaptors therefore exclude from In this work, shed light nature poly-ubiquitinated present at surface LCV provide molecular mechanism for avoidance Ub-decorated

Язык: Английский

Процитировано

6
Sde proteins coordinate ubiquitin utilization and phosphoribosylation to establish and maintain the Legionella replication vacuole DOI Creative Commons

Kristin M. Kotewicz,

Mengyun Zhang, Seongok Kim

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 30, 2024

The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification Reticulon 4 (Rtn4). have two additional activities unclear relevance the infection process: K63 linkage-specific deubiquitination and phosphoribosyl polyubiquitin (pR-Ub). We show here activity (DUB) stimulates ER while pR-Ub protects replication vacuole from cytosolic surveillance by autophagy. Loss DUB is lowered Rtn4, consistent with fueling production pR-Ub-Rtn4. In parallel, polyUb, in a region protein known as isoleucine patch, prevents binding autophagy adapter p62. An inability mutants modify polyUb results immediate p62 association, critical precursor autophagic attack. ability WT block association decays quickly after bacterial infection, predicted presence previously characterized L. effectors inactivate remove polyUb. sum, these accessory act stimulate protect innate immune sensing temporal fashion.

Язык: Английский

Процитировано

4
Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner DOI Creative Commons

Emilie Reyne,

Jeffrey Arrindell,

Eloïne Bestion

и другие.

Autophagy Reports, Год журнала: 2025, Номер 4(1)

Опубликована: Март 11, 2025

Tropheryma whipplei, the agent of Whipple's disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to formation T. whipplei replicative vacuole remain poorly understood. Macrophage microbicidal activity largely related macro/autophagy which also essential for cell homeostasis. Here, we show uptake by macrophages involved LC3-associated phagocytosis (LAP). Bacteria then escaped into cytosol from where they were recaptured xenophagy. We demonstrate blocked autophagic flux build its compartment. Inhibition LAP resulted decrease interleukin (IL)-10 secretion restoration autophagy flux, suggesting modulation during infection alters immune response promote persistence. Our results provide new insight fate bacteria macrophage suggest possible involvement previously unknown virulence factors infection.

Язык: Английский

Процитировано

0
Staphylococcus aureus reprograms CASP8 (caspase 8) signaling to evade cell death and Xenophagy DOI

Yi-Tian Ying,

Jing Yang,

Hui-Wen Ye

и другие.

Autophagy, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Regulated cell death and xenophagy constitute fundamental cellular mechanisms against invading microorganisms. Staphylococcus aureus, a notorious pathogen, can invade persist within host cells for extended periods. Here, we describe novel mechanism by which S. aureus subverts these defenses through the manipulation of CASP8 (caspase 8) signaling pathway. Upon invasion, triggers assembly RIPK3 (receptor interacting serine/threonine kinase 3) complex to induce autoprocessing. However, bacterium inhibits CUL3 (cullin 3)-dependent K63-linked ubiquitination, leading an atypical activation CASP8. This non-canonical does not initiate CASP8-CASP3 cascade but instead suppresses RIPK3-dependent necroptosis, regulated pathway typically activated when apoptosis fails. The resulting non-apoptotic, cleaved redirects its enzymatic activity toward cleaving SQSTM1/p62, selective macroautophagy/autophagy receptor, thus enabling evade antimicrobial xenophagy. results this study suggest that reprograms from inducing preserving survival inhibiting xenophagy, critical strategy supports stealthy replication persistence cells.

Язык: Английский

Процитировано

0
Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases DOI
Derek L. Bolhuis, Michael J. Emanuele, Nicholas G. Brown

и другие.

Biochemical Society Transactions, Год журнала: 2024, Номер 52(1), С. 241 - 267

Опубликована: Фев. 28, 2024

Protein ubiquitination is a post-translational modification that entails the covalent attachment of small protein ubiquitin (Ub), which acts as signal to direct stability, localization, or interactions. The Ub code written by family enzymes called E3 ligases (∼600 members in humans), can catalyze transfer either single formation diverse array polyubiquitin chains. This be edited erased different set termed deubiquitinases (DUBs; ∼100 humans). While from these distinct families have seemingly opposing activities, certain E3–DUB pairings also synergize regulate vital cellular processes like gene expression, autophagy, innate immunity, and cell proliferation. In this review, we highlight recent studies describing ligase-DUB interactions focus on their relationships.

Язык: Английский

Процитировано

2
USP14 inhibition promotes DNA damage repair and represses ovarian granulosa cell senescence in premature ovarian insufficiency DOI Creative Commons
Linzi Ma, Ao Wang,

Yun-Hui Lai

и другие.

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 11, 2024

Язык: Английский

Процитировано

2
Innate immune responses and monocyte-derived phagocyte recruitment in protective immunity to pathogenic bacteria: insights from Legionella pneumophila DOI
Danielle P. A. Mascarenhas, Dario S. Zamboni

Current Opinion in Microbiology, Год журнала: 2024, Номер 80, С. 102495 - 102495

Опубликована: Июнь 21, 2024

Язык: Английский

Процитировано

1
Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition DOI Creative Commons
Yuxin Mao, Min Wan,

Marena Minelli

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 14, 2023

Abstract Ubiquitination is a crucial posttranslational modification in eukaryotes that plays significant role the infection of intracellular microbial pathogens, such as Legionella pneumophila, bacterium responsible for Legionnaires’ disease. While Legionella-containing vacuole (LCV) coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. In this study, we report Sdc and Sde families effectors work together to build ubiquitinated species around LCV. The catalyze canonical polyubiquitination directly on host targets or phosphoribosyl-Ub (PR-Ub) conjugated Sde. Remarkably, Ub moieties within poly-Ub chains are either modified phosphoribosyl group other PDE domain-containing covalently attached substrates via Sde-mediated PR-ubiquitination. Furthermore, these modifications prevent adaptors, p62, therefore exclude adaptors from Our findings shed light nature poly-ubiquitinated present at surface LCV provide molecular mechanism avoidance Ub-decorated

Язык: Английский

Процитировано

2
Sde Proteins Coordinate Ubiquitin Utilization and Phosphoribosylation to Promote Establishment and Maintenance of the Legionella Replication Vacuole DOI Creative Commons
Ralph R. Isberg,

Kristin M. Kotewicz,

Mengyun Zheng

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 18, 2023

Abstract The Legionella pneumophilaSde family of translocated proteins promote host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification Reticulon 4 (Rtn4). Sde have two additional activities unclear relevance the infection process: K63 linkage-specific deubiquitination and phosphoribosyl polyubiquitin (pR-Ub). We show here activity (DUB) stimulates ER while pR-Ub protects replication vacuole from cytosolic surveillance by autophagy. Loss DUB was lowered Rtn4, consistent with fueling production pR-Ub-Rtn4. In parallel, polyUb, in a region protein known as isoleucine patch, caused an absolute block binding autophagy adapter p62. An inability mutants modify polyUb resulted immediate p62 association, critical precursor autophagic attack. ability WT association decayed quickly after bacterial infection, predicted presence previously characterized L. pneumophila effectors inactivate remove polyUb. sum, these results accessory act stimulate protect innate immune sensing temporal fashion.

Язык: Английский

Процитировано

1
Insights into mechanisms of ubiquitin ADP-ribosylation reversal DOI Creative Commons
Zhengrui Zhang, Chittaranjan Das

Biochemical Society Transactions, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Ubiquitination and ADP-ribosylation are two types of post-translational modification (PTM) involved in regulating various cellular activities. In a striking example direct interplay between ubiquitination ADP-ribosylation, the bacterial pathogen Legionella pneumophila uses its SidE family secreted effectors to catalyze an NAD+-dependent phosphoribosyl host substrates process involving intermediary formation ADP-ribosylated ubiquitin (ADPR-Ub). This noncanonical pathway is finely regulated by multiple ensure balanced subjugation. Among regulatory effectors, macrodomain effector MavL has been recently shown reverse Ub regenerate intact Ub. Here, we briefly outline emerging knowledge on tap into cases cross-talk these PTMs. The chemistry ADP-ribose context PTM reversal mechanisms then highlighted. Lastly, focusing recent structural studies MavL-mediated strive deduce distinct regarding catalysis product release this reaction.

Язык: Английский

Процитировано

0