The interplay between pathogens and Atg8 family proteins: thousand‐faced interactions

Tóth, Dávid; Horváth, Gábor; Juhász, Gábor

doi:10.1002/2211-5463.13318

Cited by 6 publications

(6 citation statements)

References 68 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides vIRF-1, other viral proteins that can interact with ATG8 proteins have been reported [ 8 , 38 ]. For example, the matrix protein M2 of influenza A virus has been verified experimentally to contain a conserved LIR motif, which is required for binding to and redistributing LC3 to the plasma membrane, thereby subverting antiviral autophagy (virophagy) [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy

Choi

2023

PLoS Pathog

View full text Add to dashboard Cite

Recently, viruses have been shown to regulate selective autophagy for productive infections. For instance, human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), activates selective autophagy of mitochondria, termed mitophagy, thereby inhibiting antiviral innate immune responses during lytic infection in host cells. We previously demonstrated that HHV-8 viral interferon regulatory factor 1 (vIRF-1) plays a crucial role in lytic replication-activated mitophagy by interacting with cellular mitophagic proteins, including NIX and TUFM. However, the precise molecular mechanisms by which these interactions lead to mitophagy activation remain to be determined. Here, we show that vIRF-1 binds directly to mammalian autophagy-related gene 8 (ATG8) proteins, preferentially GABARAPL1 in infected cells, in an LC3-interacting region (LIR)-independent manner. Accordingly, we identified key residues in vIRF-1 and GABARAPL1 required for mutual interaction and demonstrated that the interaction is essential for mitophagy activation and HHV-8 productive replication. Interestingly, the mitophagy receptor NIX promotes vIRF-1-GABARAPL1 interaction, and NIX/vIRF-1-induced mitophagy is significantly inhibited in GABARAPL1-deficient cells. Moreover, a vIRF-1 variant defective in GABARAPL1 binding substantially loses the ability to induce vIRF-1/NIX-induced mitophagy. These results suggest that NIX supports vIRF-1 activity as a mitophagy mediator. In addition, we found that NIX promotes vIRF-1 aggregation and stabilizes aggregated vIRF-1. Together, these findings indicate that vIRF-1 plays a role as a viral mitophagy mediator that can be activated by a cellular mitophagy receptor.

show abstract

Section: Discussionmentioning

confidence: 99%

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy

Choi

2023

PLoS Pathog

View full text Add to dashboard Cite

show abstract

“…Plant autophagy research is focused on the function in the cytoplasm where selective autophagy works [ 11 ]. However, recent studies have shown that ATG8 interacts with various proteins in the nucleus [ 74 , 75 ]. Pathogen proteins might affect autophagy activity through ATG8 interaction in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Identification and Expression Analysis of the Solanum tuberosum StATG8 Family Associated with the WRKY Transcription Factor

Song

Hong

Huh

2022

Plants

View full text Add to dashboard Cite

Autophagy is an evolutionarily well-conserved cellular catabolic pathway in eukaryotic cells and plays an important role in cellular processes. Autophagy is regulated by autophagy-associated (ATG) proteins. Among these ATG proteins, the ubiquitin-like protein ATG8/LC3 is essential for autophagosome formation and function. In this study, the potato StATG8 family showed clade I and clade II with significantly different sequences. Expression of the StATG8 family was also increased in senescence. Interestingly, the expression of the StATG8 and other core StATG genes decreased in potato tubers as the tubers matured. The StATG8 family also responded to a variety of stresses such as heat, wounding, salicylic acid, and salt stress. We also found that some Arabidopsis WRKY transcription factors interacted with the StATG8 protein in planta. Based on group II-a WRKY, StATG8-WRKY interaction is independent of the ATG8 interacting motif (AIM) or LC3 interacting region (LIR) motif. This study showed that the StATG8 family had diverse functions in tuber maturation and multiple stress responses in potatoes. Additionally, StATG8 may have an unrelated autophagy function in the nucleus with the WRKY transcription factor.

show abstract

“…The collection of a few dozen experimentally characterized LIR motifs made it possible to develop computational methods for their prediction [ 19 , 20 ]. Such prediction tools have inevitably facilitated the advancement of research toward identifying the molecular mechanisms underlying several subtypes of selective macroautophagy and related biological processes [ 21 ], and the number of scientific publications reporting the experimental validation of functional LIR motifs continues to accumulate. Despite the importance of experimentally verified LIR motifs, for wet lab biologists and computational biologists alike, there is a lack of a central repository of LIR-motif instances curated from the literature describing such sequences across species.…”

Section: Introductionmentioning

confidence: 99%

LIRcentral: a manually curated online database of experimentally validated functional LIR motifs

Chatzichristofi,

Sagris,

Pallaris

et al. 2023

Autophagy

View full text Add to dashboard Cite

Several selective macroautophagy receptor and adaptor proteins bind members of the Atg8 (autophagy related 8) family using short linear motifs (SLiMs), most often referred to as Atg8-family interacting motifs (AIMs) or LC3-interacting regions (LIRs). AIM/LIR motifs have been extensively studied during the last fifteen years, since they can uncover the underlying biological mechanisms and possible substrates for this key catabolic process of eukaryotic cells. Prompted by the fact that experimental information regarding LIR motifs can be found scattered across heterogeneous literature resources, we have developed LIRcentral ( https://lircentral.eu ), a freely available online repository for user-friendly access to comprehensive, high-quality information regarding LIR motifs from manually curated publications. Herein, we describe the development of LIRcentral and showcase currently available data and features, along with our plans for the expansion of this resource. Information incorporated in LIRcentral is useful for accomplishing a variety of research tasks, including: (i) guiding wet biology researchers for the characterization of novel instances of LIR motifs, (ii) giving bioinformaticians/computational biologists access to high-quality LIR motifs for building novel prediction methods for LIR motifs and LIR containing proteins (LIRCPs) and (iii) performing analyses to better understand the biological importance/features of functional LIR motifs. We welcome feedback on the LIRcentral content and functionality by all interested researchers and anticipate this work to spearhead a community effort for sustaining this resource which will further promote progress in studying LIR motifs/LIRCPs. Abbreviations : AIM, Atg8-family interacting motif; Atg8, autophagy related 8; GABARAP, GABA type A receptor-associated protein; LIR, LC3-interacting region; LIRCP, LIR-containing protein; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; PMID, PubMed identifier; PPI, protein-protein interaction; SLiM, short linear motif

show abstract

The interplay between pathogens and Atg8 family proteins: thousand‐faced interactions

Cited by 6 publications

References 68 publications

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy

Identification and Expression Analysis of the Solanum tuberosum StATG8 Family Associated with the WRKY Transcription Factor

LIRcentral: a manually curated online database of experimentally validated functional LIR motifs

Contact Info

Product

Resources

About