ULK1 targets Beclin-1 in autophagy

Nazarko, Volodymyr Y.; Zhong, Qing

doi:10.1038/ncb2797

Cited by 74 publications

(61 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The autophagyrelated (ATG) proteins compose several core components of autophagy, which are required for autophagosome formation (24,25). mTORC1 (mammalian target of rapamycin complex 1) kinase is a key negative regulator of the ULK1 complex (Unc-51-like autophagy activating kinase 1), which is made up of ULK1, ATG101, ATG13, and RB1CC1/FIP200 (26)(27)(28)(29)(30) and serves as the initiator in the autophagic cascade. The class III phosphatidylinositol 3-kinase (PI3K) complex (BECN1/Beclin1-ATG14-VPS15-VPS34) and two other conjugation systems, ATG12 (ATG12-ATG5-ATG16) and LC3/ATG8, operate downstream of ULK-1 (31,32).…”

mentioning

confidence: 99%

Autophagy Promotes Replication of Influenza A Virus In Vitro

Wang

Zhu

Zhao

et al. 2019

J Virol

View full text Add to dashboard Cite

Influenza A virus (IAV) infection could induce autophagosome accumulation. However, the impact of the autophagy machinery on IAV infection remains controversial. Here, we showed that induction of cellular autophagy by starvation or rapamycin treatment increases progeny virus production, while disruption of autophagy using a small interfering RNA (siRNA) and pharmacological inhibitor reduces progeny virus production. Further studies revealed that alteration of autophagy significantly affects the early stages of the virus life cycle or viral RNA synthesis. Importantly, we demonstrated that overexpression of both the IAV M2 and NP proteins alone leads to the lipidation of LC3 to LC3-II and a redistribution of LC3 from the cytosol to punctate vesicles indicative of authentic autophagosomes. Intriguingly, both M2 and NP colocalize and interact with LC3 puncta during M2 or NP transfection alone and IAV infection, leading to an increase in viral ribonucleoprotein (vRNP) export and infectious viral particle formation, which indicates that the IAV-host autophagy interaction plays a critical role in regulating IAV replication. We showed that NP and M2 induce the AKT-mTOR-dependent autophagy pathway and an increase in HSP90AA1 expression. Finally, our studies provided evidence that IAV replication needs an autophagy pathway to enhance viral RNA synthesis via the interaction of PB2 and HSP90AA1 by modulating HSP90AA1 expression and the AKT-mTOR signaling pathway in host cells. Collectively, our studies uncover a new mechanism that NP-and M2-mediated autophagy functions in different stages of virus replication in the pathogenicity of influenza A virus. IMPORTANCE Autophagy impacts the replication cycle of many viruses. However, the role of the autophagy machinery in IAV replication remains unclear. Therefore, we explored the detailed mechanisms utilized by IAV to promote its replication. We demonstrated that IAV NP-and M2-mediated autophagy promotes IAV replication by regulating the AKT-mTOR signaling pathway and HSP90AA1 expression. The interaction of PB2 and HSP90AA1 results in the increase of viral RNA synthesis first; subsequently the binding of NP to LC3 favors vRNP export, and later the interaction of M2 and LC3 leads to an increase in the production of infectious viral particles, thus accelerating viral progeny production. These findings improve our understanding of IAV pathogenicity in host cells.

show abstract

mentioning

confidence: 99%

Autophagy Promotes Replication of Influenza A Virus In Vitro

Wang

Zhu

Zhao

et al. 2019

J Virol

View full text Add to dashboard Cite

show abstract

“…However, in our study, we found that increased TXNIP had no influence on AMPK phosphorylation. Beclin 1 also has a central role in autophagy, by interacting with Vps34 to induce autophagy . We found that overexpression of TXNIP had no impact on Beclin 1 expression.…”

Section: Discussionmentioning

confidence: 68%

Thioredoxin‐interacting protein induced α‐synuclein accumulation via inhibition of autophagic flux: Implications for Parkinson's disease

Liu

et al. 2017

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…In mammals a direct phosphorylation interaction between ULK1/Atg1 and Beclin 1 was recently found, strengthening further the importance of Beclin 1 in autophagy induction30. As Beclin 1 could serve as an alternative autophagy inducer in non-unikont protists, we searched for and could identify possible Beclin 1 orthologs in the half of these species (Suppl.…”

Section: Resultsmentioning

confidence: 77%

Starvation-response may not involve Atg1-dependent autophagy induction in non-unikont parasites

Földvári-Nagy

Ari

Csermely

et al. 2014

Sci Rep

View full text Add to dashboard Cite

Autophagy, the lysosome-mediated self-degradation process, is implicated in survival during starvation in yeast, Dictyostelium and animals. In these eukaryotic taxa (collectively called Unikonts), autophagy is induced primarily through the Atg1/ULK1 complex in response to nutrient depletion. Autophagy has also been well-studied in non-unikont parasites, such as Trypanosoma and Plasmodium, and found important in their life-cycle transitions. However, how autophagy is induced in non-unikonts remains largely unrevealed. Using a bioinformatics approach, we examined the presence of Atg1 and of its complex in the genomes of 40 non-unikonts. We found that these genomes do not encode typical Atg1 proteins: BLAST and HMMER queries matched only with the kinase domain of Atg1, while other segments responsible for regulation and protein-binding were missing. Non-unikonts also lacked other components of the Atg1-inducing complex. Orthologs of an alternative autophagy inducer, Atg6 were found only in the half of the species, indicating that the other half may possess other inducing mechanisms. As key autophagy genes have differential expression patterns during life-cycle, we raise the possibility that autophagy in these protists is induced mainly at the post-transcriptional level. Understanding Atg1-independent autophagy induction mechanisms in these parasites may lead to novel pharmacological interventions, not affecting human Atg1-dependent autophagy.

show abstract

ULK1 targets Beclin-1 in autophagy

Cited by 74 publications

References 15 publications

Autophagy Promotes Replication of Influenza A Virus In Vitro

Autophagy Promotes Replication of Influenza A Virus In Vitro

Thioredoxin‐interacting protein induced α‐synuclein accumulation via inhibition of autophagic flux: Implications for Parkinson's disease

Starvation-response may not involve Atg1-dependent autophagy induction in non-unikont parasites

Contact Info

Product

Resources

About