BAG3 promotes autophagy and glutaminolysis via stabilizing glutaminase

Zhao, Song; Wang, Jiamei; Yan, Jun; Zhang, Dalin; Liu, Bao-Qin; Jiang, Jingyi; Li, Chao; Li, Si; Meng, Xiangchuan; Wang, Hua‐Qin

doi:10.1038/s41419-019-1504-6

Cited by 46 publications

(50 citation statements)

References 41 publications

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“…Glutamine can be converted via GLS to glutamate, which can subsequently be converted to αketoglutarate to fuel the TCA cycle. Succinylation of GLS suppresses its K48-linked ubiquitination and degradation, stabilizing GLS and promoting glutaminolysis in cancer cells [295]. Study also found the function of supranutritional dose of selenite in suppressing tumor progression by promoting APC/C-CDH1 mediated GLS1 ubiquitination and degradation [296].…”

Section: Ubiquitination and Amino Acid Metabolismmentioning

confidence: 76%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

256

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Section: Ubiquitination and Amino Acid Metabolismmentioning

confidence: 76%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

256

178

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“…Given their complimentary roles in autophagy (i.e., BAG3) and proteasomal degradation (i.e., BAG1), we next determined whether a downregulation in BAG3 was associated with a compensatory upregulation of BAG1 51 , 52 . In primary neurons expressing either Tat or Nef, no significant variation in BAG1 protein was observed, either by immunoblot or fluorescent microscopy (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neuromodulation of BAG co-chaperones by HIV-1 viral proteins and H2O2: implications for HIV-associated neurological disorders

et al. 2021

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Despite increasing numbers of aged individuals living with HIV, the mechanisms underlying HIV-associated neurological disorders (HANDs) remain elusive. As HIV-1 pathogenesis and aging are characterized by oxidative stress as well as altered protein quality control (PQC), reactive oxygen species (ROS) themselves might constitute a molecular mediator of neuronal PQC by modulating BCL-2 associated athanogene (BAG) family members. Present results reveal H2O2 replicated and exacerbated a reduction in neuronal BAG3 induced by the expression of HIV-1 viral proteins (i.e., Tat and Nef), while also causing an upregulation of BAG1. Such a reciprocal regulation of BAG3 and BAG1 levels was also indicated in two animal models of HIV, the doxycycline-inducible Tat (iTat) and the Tg26 mouse. Inhibiting oxidative stress via antioxidants in primary culture was capable of partially preserving neuronal BAG3 levels as well as electrophysiological functioning otherwise altered by HIV-1 viral proteins. Current findings indicate HIV-1 viral proteins and H2O2 may mediate neuronal PQC by exerting synergistic effects on complementary BAG family members, and suggest novel therapeutic targets for the aging HIV-1 population.

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“…For example, we observed significant changes in the expression of Bcl-2 associated athanogene (Bag) proteins, which increase client release from Hsp70 by accelerating nucleotide exchange at the ATP site of this folding chaperone, in both naïve (ON) and influenza challenged (OF) aged cells. Here, we observed a striking difference in the expression pattern of Bag3 (Fig 10A, lower panel, black arrow), which is involved in regulating autophagy pathways (14,(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77),…”

Section: Folding Components Differentially Regulated By Aging and Infmentioning

confidence: 93%

Proteostasis and Energetics as Proteome Hallmarks of Aging and Influenza Challenge in Pulmonary Disease

Loguercio

Hutt

Campos

et al. 2019

Preprint

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Aging is associated with an increased risk for the development of many diseases. This is exemplified by the increased incidence of lung injury, muscle dysfunction and cognitive impairment in the elderly following influenza infection. Because the infectious cycle of flu is dependent upon the properties of the host, we examined the proteome of alveolar macrophages (AM) and type 2 cells (AT2) obtained from young (3 months) and old (18 months) naïve mice and mice exposed to influenza A. Our proteomics data show that there is a maladaptive collapse of the proteostasis network (PN) and changes in mitochondrial pathways in the aged naïve AM and AT2 proteomes. The mitochondrial imbalance and proteostatic collapse seen in aged cells places an excessive folding burden on these cells, which is further exacerbated following exposure to influenza A. Specifically, we see an imbalance in Hsp70 co-chaperones involved in protein folding and Hsp90 co-chaperones important for stress signaling pathways that are essential for cellular protection during aging. The acute challenge of influenza A infection of young and aged AM and AT2 cells reveals that age-associated changes in the chaperome affect the ability of these cells to properly manage the infection and post-infection biology, contributing to cytotoxicity. We posit that proteomic profiling of individual cell type specific responses provides a high impact approach to pinpoint fundamental molecular relationships that may contribute to the susceptibility to aging and environmental stress, providing a platform to identify new targets for therapeutic intervention to improve resiliency in the elderly.

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BAG3 promotes autophagy and glutaminolysis via stabilizing glutaminase

Cited by 46 publications

References 41 publications

The role of ubiquitination and deubiquitination in cancer metabolism

The role of ubiquitination and deubiquitination in cancer metabolism

Neuromodulation of BAG co-chaperones by HIV-1 viral proteins and H2O2: implications for HIV-associated neurological disorders

Proteostasis and Energetics as Proteome Hallmarks of Aging and Influenza Challenge in Pulmonary Disease

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