The matrix protein of lyssavirus hijacks autophagosome for efficient egress by recruiting NEDD4 through its PPxY motif
In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular viru...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Yueming Yuan An Fang Zhihui Wang Huanchun Chen Zhen F Fu Ming Zhou Ling Zhao Source Type: research
ATF6 supports lysosomal function in tumor cells to enable ER stress-activated macroautophagy and CMA: impact on mutant TP53 expression
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338577. Online ahead of print.ABSTRACTThe inhibition of the unfolded protein response (UPR), which usually protects cancer cells from stress, may be exploited to potentiate the cytotoxic effect of drugs inducing ER stress. However, in this study, we found that ER stress and UPR activation by thapsigargin or tunicamycin promoted the lysosomal degradation of mutant (MUT) TP53 and that the inhibition of the UPR sensor ATF6, but not of ERN1/IRE1 or EIF2AK3/PERK, counteracted such an effect. ATF6 activation was indeed required to sustain the function of lysosomes, enabling the ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Rossella Benedetti Maria Anele Romeo Andrea Arena Maria Saveria Gilardini Montani Gabriella D'Orazi Mara Cirone Source Type: research
LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 < sup > + < /sup > T lymphocytes
Autophagy. 2024 Apr 7:1-12. doi: 10.1080/15548627.2024.2338573. Online ahead of print.ABSTRACTHIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4+ T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown. Here we found that HIV-1 exposure lead...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Baptiste Pradel Guilhem Cantaloube Marie Villares Ma ïka S Deffieu V éronique Robert-Hebmann Vincent Lucansky Mathias Faure Nathalie Chazal Rapha ël Gaudin Lucile Espert Source Type: research
The matrix protein of lyssavirus hijacks autophagosome for efficient egress by recruiting NEDD4 through its PPxY motif
In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular viru...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Yueming Yuan An Fang Zhihui Wang Huanchun Chen Zhen F Fu Ming Zhou Ling Zhao Source Type: research
ATF6 supports lysosomal function in tumor cells to enable ER stress-activated macroautophagy and CMA: impact on mutant TP53 expression
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338577. Online ahead of print.ABSTRACTThe inhibition of the unfolded protein response (UPR), which usually protects cancer cells from stress, may be exploited to potentiate the cytotoxic effect of drugs inducing ER stress. However, in this study, we found that ER stress and UPR activation by thapsigargin or tunicamycin promoted the lysosomal degradation of mutant (MUT) TP53 and that the inhibition of the UPR sensor ATF6, but not of ERN1/IRE1 or EIF2AK3/PERK, counteracted such an effect. ATF6 activation was indeed required to sustain the function of lysosomes, enabling the ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Rossella Benedetti Maria Anele Romeo Andrea Arena Maria Saveria Gilardini Montani Gabriella D'Orazi Mara Cirone Source Type: research
LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 < sup > + < /sup > T lymphocytes
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338573. Online ahead of print.ABSTRACTHIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4+ T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown. Here we found that HIV-1 exposure leads to ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Baptiste Pradel Guilhem Cantaloube Marie Villares Ma ïka S Deffieu V éronique Robert-Hebmann Vincent Lucansky Mathias Faure Nathalie Chazal Rapha ël Gaudin Lucile Espert Source Type: research
The matrix protein of lyssavirus hijacks autophagosome for efficient egress by recruiting NEDD4 through its PPxY motif
In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular viru...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Yueming Yuan An Fang Zhihui Wang Huanchun Chen Zhen F Fu Ming Zhou Ling Zhao Source Type: research
ATF6 supports lysosomal function in tumor cells to enable ER stress-activated macroautophagy and CMA: impact on mutant TP53 expression
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338577. Online ahead of print.ABSTRACTThe inhibition of the unfolded protein response (UPR), which usually protects cancer cells from stress, may be exploited to potentiate the cytotoxic effect of drugs inducing ER stress. However, in this study, we found that ER stress and UPR activation by thapsigargin or tunicamycin promoted the lysosomal degradation of mutant (MUT) TP53 and that the inhibition of the UPR sensor ATF6, but not of ERN1/IRE1 or EIF2AK3/PERK, counteracted such an effect. ATF6 activation was indeed required to sustain the function of lysosomes, enabling the ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Rossella Benedetti Maria Anele Romeo Andrea Arena Maria Saveria Gilardini Montani Gabriella D'Orazi Mara Cirone Source Type: research
LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 < sup > + < /sup > T lymphocytes
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338573. Online ahead of print.ABSTRACTHIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4+ T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown. Here we found that HIV-1 exposure leads to ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Baptiste Pradel Guilhem Cantaloube Marie Villares Ma ïka S Deffieu V éronique Robert-Hebmann Vincent Lucansky Mathias Faure Nathalie Chazal Rapha ël Gaudin Lucile Espert Source Type: research
The matrix protein of lyssavirus hijacks autophagosome for efficient egress by recruiting NEDD4 through its PPxY motif
In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular viru...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Yueming Yuan An Fang Zhihui Wang Huanchun Chen Zhen F Fu Ming Zhou Ling Zhao Source Type: research
ATF6 supports lysosomal function in tumor cells to enable ER stress-activated macroautophagy and CMA: impact on mutant TP53 expression
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338577. Online ahead of print.ABSTRACTThe inhibition of the unfolded protein response (UPR), which usually protects cancer cells from stress, may be exploited to potentiate the cytotoxic effect of drugs inducing ER stress. However, in this study, we found that ER stress and UPR activation by thapsigargin or tunicamycin promoted the lysosomal degradation of mutant (MUT) TP53 and that the inhibition of the UPR sensor ATF6, but not of ERN1/IRE1 or EIF2AK3/PERK, counteracted such an effect. ATF6 activation was indeed required to sustain the function of lysosomes, enabling the ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Rossella Benedetti Maria Anele Romeo Andrea Arena Maria Saveria Gilardini Montani Gabriella D'Orazi Mara Cirone Source Type: research
LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 < sup > + < /sup > T lymphocytes
Autophagy. 2024 Apr 2. doi: 10.1080/15548627.2024.2338573. Online ahead of print.ABSTRACTHIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4+ T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown. Here we found that HIV-1 exposure leads to ...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Baptiste Pradel Guilhem Cantaloube Marie Villares Ma ïka S Deffieu V éronique Robert-Hebmann Vincent Lucansky Mathias Faure Nathalie Chazal Rapha ël Gaudin Lucile Espert Source Type: research
The matrix protein of lyssavirus hijacks autophagosome for efficient egress by recruiting NEDD4 through its PPxY motif
In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular viru...
Source: Autophagy - April 3, 2024 Category: Cytology Authors: Yueming Yuan An Fang Zhihui Wang Huanchun Chen Zhen F Fu Ming Zhou Ling Zhao Source Type: research
TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging
Autophagy. 2024 Mar 28:1-10. doi: 10.1080/15548627.2024.2333717. Online ahead of print.ABSTRACTSarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and...
Source: Autophagy - March 28, 2024 Category: Cytology Authors: David Sebasti án Marc Beltr à Andrea Irazoki David Sala Pilar Aparicio Cecilia Aris Esmaeil Alibakhshi Maria Rubio-Valera Manuel Palac ín Juan Castellanos Luis Lores Antonio Zorzano Source Type: research
TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging
Autophagy. 2024 Mar 28:1-10. doi: 10.1080/15548627.2024.2333717. Online ahead of print.ABSTRACTSarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and...
Source: Autophagy - March 28, 2024 Category: Cytology Authors: David Sebasti án Marc Beltr à Andrea Irazoki David Sala Pilar Aparicio Cecilia Aris Esmaeil Alibakhshi Maria Rubio-Valera Manuel Palac ín Juan Castellanos Luis Lores Antonio Zorzano Source Type: research
