Participation of proteasome-ubiquitin protein degradation in autophagy and the activation of AMP-activated protein kinase

Jiang, Shaoning; Park, Dae Won; Gao, Yong; Ravi, Saranya; Darley‐Usmar, Victor; Abraham, Edward; Żmijewski, Jaroslaw W.

doi:10.1016/j.cellsig.2015.02.024

Cited by 33 publications

(24 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that AMPK has three major upstream kinases: LKB1, CaMKKb, and TAK1, each of which is activated by different stimuli and in various tissues resulting in diverse outcomes [1,7]. Furthermore, the possibility of crosstalk between AMPK and UPS adds another layer of complexity to the system [29][30][31][32][33]. Considering the importance of AMPK and UPS signaling as two major anticancer strategies, it is important to understand their crosstalk.…”

Section: Discussionmentioning

confidence: 99%

Proteasome inhibitors induce AMPK activation via CaMKKβ in human breast cancer cells

Deshmukh

Dou

2015

Breast Cancer Res Treat

View full text Add to dashboard Cite

The purpose of present study is to examine the mechanism of the 5'-AMP-activated protein kinase (AMPK) activation induced by proteasome inhibitors. AMPK activation and ubiquitin proteasome system (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. However, the relationship between these two important pathways is not very clear. We observe that proteasome inhibition leads to AMPK activation in human breast cancer cells. siRNA transfection, western blotting, qPCR, and proteasomal inhibition assays were used to study the mechanism of proteasome inhibitor-induced AMPK activation using human triple-negative breast cancer, lung, and cervical cancer cell lines. We report that a variety of proteasome inhibitors activate AMPK in all the tested different cancer cell lines. Our data using liver kinase B1-deficient cancer cells suggest that proteasome inhibitor-induced AMPK activation is primarily mediated by Calcium/Calmodulin-dependent kinase kinase β (CaMKKβ). This hypothesis is supported by that pharmacological or genetic inhibition of CaMKKβ leads to a decrease in proteasome inhibitor-induced AMPK activation. Additionally, the AMPK-activating function of the FDA-approved proteasome inhibitor bortezomib depends on an increase in intracellular calcium levels as calcium chelation abrogates its induced AMPK activation. Finally, bortezomib-mediated upregulation in CaMKKβ levels is due to its enhanced protein synthesis. These data suggest that proteasome inhibitors indirectly activate AMPK in human cancer cells primarily via Ca(2+)-CaMKKβ-dependent pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteasome inhibitors induce AMPK activation via CaMKKβ in human breast cancer cells

Deshmukh

Dou

2015

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…In cultured mammalian cells, UPS inhibition has been reported to activate AMPK, possibly through relieving proteasomal degradation of AMPK subunits (Jiang et al, 2015; Zungu et al, 2011). Two likely possibilities exist to explain why this phenomenon is not orthologous between cells in culture and C. elegans , 1) that cells in culture are not representative of in vivo signaling and physiology and/or 2) that UPS inhibition of AMPK in C. elegans involves a multi-tissue signaling relay.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide RNAi Screen for Fat Regulatory Genes in C. elegans Identifies a Proteostasis-AMPK Axis Critical for Starvation Survival

et al. 2017

View full text Add to dashboard Cite

SUMMARY Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans to identify fat regulatory genes indispensable for starvation resistance. Here we show that opposing proteostasis pathways are principal determinants of starvation survival. Reduced function of cytoplasmic amino-acyl tRNA synthetases (ARS) increases fat mass and extends starvation survival, whereas reduced proteasomal function reduces fat and starvation survival. These opposing pathways converge on AMP-activated protein kinase (AMPK) as the critical effector of starvation defenses. Extended starvation survival in ARS deficiency is dependent upon increased proteasome-mediated activation of AMPK. When the proteasome is inhibited, neither starvation nor ARS deficiency can fully activate AMPK, leading to greatly diminished starvation survival. Thus, activity of the proteasome and AMPK are mechanistically linked and highly correlated with starvation resistance. Conversely, aberrant activation of the proteostasis-AMPK axis during nutritional excess may have implications for obesity and cardiometabolic diseases.

show abstract

“…Peritoneal macrophages were isolated, as previously described [32]. Macrophages were elicited in 10-12-wk-old mice by i.p.…”

Section: Peritoneal Macrophages Neutrophils and Monocytes Isolationmentioning

confidence: 99%

Frontline Science: D1 dopaminergic receptor signaling activates the AMPK-bioenergetic pathway in macrophages and alveolar epithelial cells and reduces endotoxin-induced ALI

Bone

Liu

Pittet

et al. 2016

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

Catecholamines, including β-adrenergic and dopaminergic neurotransmitters, have an essential role in regulating the "fight or flight" reflex and also affects immune cell proinflammatory action. However, little is known about whether catecholamines prevent dysfunction of metabolic pathways associated with inflammatory organ injury, including development of acute lung injury (ALI). We hypothesize that selected catecholamines may reduce metabolic alterations in LPS-stimulated macrophages and in the lungs of mice subjected to endotoxin-induced ALI, a situation characterized by diminished activity of AMP-activated protein kinase (AMPK). We found that activation of the dopamine 1 receptor (D1R) with fenoldopam, but not stimulation of adrenergic receptors with norepinephrine, resulted in a robust activation of AMPK in peritoneal macrophages, human monocytes, or alveolar epithelial cells (AECs). Such AMPK activation was mediated by a phospholipase C (PLC)-dependent mechanism. Unlike norepinephrine, D1R activation also prevented Thr172-AMPK dephosphorylation and kinase inactivation in LPS-treated macrophages. Furthermore, we show that a culture of AECs with either fenoldopam or the AMPK activator metformin effectively diminished IL-1β-induced release of adverse paracrine signaling, which promotes the macrophage proinflammatory response. In vivo, fenoldopam reduced the severity of LPS-induced ALI, including development of pulmonary edema, lung permeability, and production of inflammatory cytokines TNF-α, MIP-2, or KC and HMGB1. Fenoldopam also prevented AMPK dephosphorylation in the lungs of LPS-treated mice and prevented loss of mitochondrial complexes NDUFB8 (complex I) and ATP synthase (complex V). Collectively, these results suggest that dopamine is coupled to AMPK activation, which provides a substantial anti-inflammatory and bioenergetic advantage and reduces the severity of endotoxin-induced ALI.

show abstract

Participation of proteasome-ubiquitin protein degradation in autophagy and the activation of AMP-activated protein kinase

Cited by 33 publications

References 71 publications

Proteasome inhibitors induce AMPK activation via CaMKKβ in human breast cancer cells

Proteasome inhibitors induce AMPK activation via CaMKKβ in human breast cancer cells

Genome-wide RNAi Screen for Fat Regulatory Genes in C. elegans Identifies a Proteostasis-AMPK Axis Critical for Starvation Survival

Frontline Science: D1 dopaminergic receptor signaling activates the AMPK-bioenergetic pathway in macrophages and alveolar epithelial cells and reduces endotoxin-induced ALI

Contact Info

Product

Resources

About