LAMTOR2/LAMTOR1 complex is required for TAX1BP1‐mediated xenophagy

Lin, Ching Yu; Nozawa, Takashi; Minowa‐Nozawa, Atsuko; Toh, Hirotaka; Aikawa, Chihiro; Nakagawa, Ichirô

doi:10.1111/cmi.12981

Cited by 23 publications

(21 citation statements)

References 32 publications

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“…Many viruses have thus evolved mechanisms to maintain mTORC1 activity during infection 35 . Recent work has shown that the LAMTOR1/2 proteins may also play important roles in xenophagy 36 .…”

Section: Crosstalk With Other Organelles and Host Protein Machines Cmentioning

confidence: 99%

A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

St-Germain

Astori

Samavarchi-Tehrani

et al. 2020

Preprint

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SummaryKey steps of viral replication take place at host cell membranes, but the detection of membrane-associated protein-protein interactions using standard affinity-based approaches (e.g. immunoprecipitation coupled with mass spectrometry, IP-MS) is challenging. To learn more about SARS-CoV-2 - host protein interactions that take place at membranes, we utilized a complementary technique, proximity-dependent biotin labeling (BioID). This approach uncovered a virus-host topology network comprising 3566 proximity interactions amongst 1010 host proteins, highlighting extensive virus protein crosstalk with: (i) host protein folding and modification machinery; (ii) membrane-bound vesicles and organelles, and; (iii) lipid trafficking pathways and ER-organelle membrane contact sites. The design and implementation of sensitive mass spectrometric approaches for the analysis of complex biological samples is also important for both clinical and basic research proteomics focused on the study of COVID-19. To this end, we conducted a mass spectrometry-based characterization of the SARS-CoV-2 virion and infected cell lysates, identifying 189 unique high-confidence virus tryptic peptides derived from 17 different virus proteins, to create a high quality resource for use in targeted proteomics approaches. Together, these datasets comprise a valuable resource for MS-based SARS-CoV-2 research, and identify novel virus-host protein interactions that could be targeted in COVID-19 therapeutics.

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Section: Crosstalk With Other Organelles and Host Protein Machines Cmentioning

confidence: 99%

A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

St-Germain

Astori

Samavarchi-Tehrani

et al. 2020

Preprint

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“…In addition, they identified LAMTOR2 and LAMTOR1 as previously overlooked xenophagy regulators of TAX1BP1 in response to Salmonella infection, and confirmed that LAMTOR2 was recruited to damaged SCVs via LAMTOR1, an endosomeresident protein. LAMTOR2 was critical for the subsequent recruitment of TAX1BP1, thus accelerating the formation of autolysosomes during bacterial infection (Lin et al, 2019).…”

Section: Adaptors Of Salmonella Autophagymentioning

confidence: 99%

Salmonella Interacts With Autophagy to Offense or Defense

Shen

Zhang

et al. 2020

Front. Microbiol.

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Autophagy is an important component of the innate immune system in mammals. Low levels of basic autophagy are sustained in normal cells, to help with the clearance of aging organelles and misfolded proteins, thus maintaining their structural and functional stability. However, when cells are faced with challenges, such as starvation or pathogenic infection, their level of autophagy increases significantly. Salmonella is a facultative intracellular pathogen, which imposes an economic burden on the poultry farming industry and human public health. Previous studies have shown that Salmonella can induce the autophagy of cells following invasion, which to a certain extent helps to protect the cells from bacterial colonization. This review summarizes the latest research in the field of Salmonella-induced autophagy, including: (i) the autophagy induction and escape mechanisms employed by Salmonella during the infection of host cells; (ii) the effect of autophagy on intracellular Salmonella; (iii) the important autophagy adaptors that recognize intracellular Salmonella in host cells; and (iv) the effect of autophagy-modulating drugs on Salmonella infection.

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“…Numerous studies have veri ed the signi cance of two signaling pathway in the progression of breast cancer. In addition, Lin and his colleagues have reported that LAMTOR2 interacted with SQSTM1 and was required for recruiting TAX1BP1 to autophagosomes (30). However, to the best of our knowledge, there is no study about the associated between LAMTOR2 and SQSTM1 in breast cancer and the underlying regulation network requires further investigations.…”

Section: Discussionmentioning

confidence: 95%

Prognostic Significance of SQSTM1 in Breast Cancer: A Comprehensive Analysis

Liu

Sun

et al. 2020

Preprint

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Background: SQSTM1 (Sequestosome 1, p62) is degraded by activated autophagy and involved in the progression of in various types of cancers. However, the prognostic role and underlying regulation mechanism of SQSTM1 in the progression and development of breast cancer remain unclear.Methods: In this study, 1336 samples with available mRNA data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database and 27 formalin fixation and paraffin embedding (FFPE) tissue samples from the First Affiliated Hospital of Xi’an Jiaotong University were collected to evaluate SQSTM1 expression in mRNA and protein levels. Kaplan–Meier and Cox regression were used for revealing prognostic value in three independent breast cancer independent datasets. Tumor Immune Estimation Resource (TIMER) database and Gene Set Variation Analysis (GSVA) was used to explore the relationship of SQSTM1 mRNA expression and immune infiltration level in breast cancer. Dysregulation mechanisms of SQSTM1 were also explored including copy number variation (CNV), somatic mutation, epigenetic alterations and other transcription and post-transcription level using multiple datasets. Finally, Gene Set Enrichment Analysis (GSEA) was constructed to elucidate functional regulating performance of SQSTM1 in breast cancer.Results: The results showed that mRNA and protein level of SQSTM1 were significantly elevated in breast cancer and receiver operating characteristic (ROC) curve showed that p62 may act as diagnostic biomarker. Lower expression of SQSTM1 predicted better outcome through multiple datasets. It was also found that SQSTM1 correlated with immune infiltrates in breast cancer. Moreover, CNV and methylation of SQSTM1 DNA was correlated with SQSTM1 dysregulation and act as prognostic factors for breast cancer patients. Yet, somatic mutation status of SQSTM1 didn’t show any prognostic relevance. We also identified diverse transcription factors that directly bound to SQSTM1 DNA and the miRNAs which may regulate SQSTM1 mRNA. Finally, functional enrichment analysis revealed that SQSTM1 is related to cell signal transduction, oxidative stress and autophagy in breast cancer.Conclusion: Our findings revealed that overexpression of SQSTM1 significantly to poor survival and immune infiltrations in breast cancer. In addition, SQSTM1 plays a key role in the progression of breast cancer and might be a promising biomarker for the diagnosis and personalized treatment of breast cancer patients.

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LAMTOR2/LAMTOR1 complex is required for TAX1BP1‐mediated xenophagy

Cited by 23 publications

References 32 publications

A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

Salmonella Interacts With Autophagy to Offense or Defense

Prognostic Significance of SQSTM1 in Breast Cancer: A Comprehensive Analysis

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