The intrinsic proteostasis network of stem cells

Llamas, Ernesto; Alirzayeva, Hafiza; Loureiro, Rute

doi:10.1016/j.ceb.2020.08.005

Cited by 20 publications

(14 citation statements)

References 69 publications

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“…Proteostasis in multicellular organisms is differentially affected during all stages of life by processes such as development and differentiation, metabolic changes, immune responses, and aging (Garcia-Prat et al, 2017; Hipp et al, 2019; Llamas et al, 2020). Therefore, sophisticated mechanisms of tissue and cell-specific proteostatic pathways to adapt to changing conditions are fundamental to prevent protein aggregation, inclusion body formation, and ultimately cell death.…”

Section: Discussionmentioning

confidence: 99%

DDI2 protease activity controls embryonic development and inflammation via TCF11/NRF1

Sivá

Procházková

Procházka

et al. 2020

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DDI2 is an aspartic protease that cleaves polyubiquitinated substrates. Upon proteotoxic stress, DDI2 activates the ER-bound transcription factor TCF11/NRF1 (NFE2L1), a master regulator of proteostasis maintenance in mammalian cells, and ensures the expression of rescue factors including proteasome subunits. Here we describe the consequences of DDI2 ablation both in vivo and in cells. Knock-out of DDI2 in mice resulted in embryonic lethality at E12.5 with severe developmental failure. Molecular characterization of the embryos and surrogate DDI2 knock-out cell lines showed insufficient proteasome expression with proteotoxic stress, accumulation of high molecular weight ubiquitin conjugates, and induction of the unfolded protein and integrated stress responses. We also show that DDI2 KO-induced proteotoxic stress causes the cell-autonomous innate immune system to induce a type I interferon signature. These results indicate an important role for DDI2 in the proteostasis network of cells and tissues and in the maintenance of a balanced immune response.

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Section: Discussionmentioning

confidence: 99%

DDI2 protease activity controls embryonic development and inflammation via TCF11/NRF1

Sivá

Procházková

Procházka

et al. 2020

Preprint

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“…Whereas a collapse in the proteostasis of terminally differentiated cells can lead to disease, human, and mouse stem cells exhibit an enhanced ability to correct proteostatic deficiencies. For instance, pluripotent and adult stem cells have increased proteolytic systems and expression of distinct chaperones to prevent protein misfolding and aggregation (Leeman et al, 2018 ; Llamas et al, 2020 ; Noormohammadi et al, 2016 , 2018 ; Prinsloo et al, 2009 ; Thiruvalluvan et al, 2020 ; Vilchez et al, 2012 , 2013 ; Vonk et al, 2020 ). Interestingly, mimicking proteostasis of human pluripotent stem cells by ectopically increasing CCT8 in somatic tissues can suppress the aggregation of disease‐related proteins such as polyQ‐expanded huntingtin, the mutant protein underlying Huntington's disease (Noormohammadi et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress

et al. 2021

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The biological purpose of plant stem cells is to maintain themselves while providing new pools of differentiated cells that form organs and rejuvenate or replace damaged tissues. Protein homeostasis or proteostasis is required for cell function and viability. However, the link between proteostasis and plant stem cell identity remains unknown. In contrast to their differentiated counterparts, we find that root stem cells can prevent the accumulation of aggregated proteins even under proteotoxic stress conditions such as heat stress or proteasome inhibition. Notably, root stem cells exhibit enhanced expression of distinct chaperones that maintain proteome integrity. Particularly, intrinsic high levels of the T‐complex protein‐1 ring complex/chaperonin containing TCP1 (TRiC/CCT) complex determine stem cell maintenance and their remarkable ability to suppress protein aggregation. Overexpression of CCT8, a key activator of TRiC/CCT assembly, is sufficient to ameliorate protein aggregation in differentiated cells and confer resistance to proteotoxic stress in plants. Taken together, our results indicate that enhanced proteostasis mechanisms in stem cells could be an important requirement for plants to persist under extreme environmental conditions and reach extreme long ages. Thus, proteostasis of stem cells can provide insights to design and breed plants tolerant to environmental challenges caused by the climate change.

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“…Several studies indicate that increased proteostasis is a stem cell hallmark, which is gradually lost upon differentiation ( Llamas et al, 2020 ). Specifically, increased proteasome activity in human embryonic stem cells (hESCs) is required to maintain both pluripotency and their ability to differentiate into specific cell lineages ( Vilchez et al, 2014 ).…”

Section: Ups and The Regulation Of Satellite Cell Functionmentioning

confidence: 99%

“…In this context, a balance between stemness and differentiation is crucial for SC function and several extrinsic and intrinsic pathways have been described to regulate these processes. In recent years, the role of protein homeostasis (proteostasis) in the regulation of stem cell function has become an exciting area of research as many studies suggest this process is particularly robust in embryonic, pluripotent and adult stem cells, while loss of proteostasis affects stemness and differentiation potential in pathological conditions and during aging ( Vilchez et al, 2014 ; Lee et al, 2017 ; Fernando et al, 2018 ; Llamas et al, 2020 ). Among different mechanisms regulating protein homeostasis, the ubiquitin-proteasome system (UPS) is one of the best described.…”

Section: Introductionmentioning

confidence: 99%

The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

Olguín

2022

Front. Cell Dev. Biol.

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In recent years, the ubiquitin-proteasome system (UPS) has emerged as an important regulator of stem cell function. Here we review recent findings indicating that UPS also plays critical roles in the biology of satellite cells, the muscle stem cell responsible for its maintenance and regeneration. While we focus our attention on the control of key transcriptional regulators of satellite cell function, we briefly discuss early studies suggesting the UPS participates more broadly in the regulation of satellite cell stemness and regenerative capacity.

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The intrinsic proteostasis network of stem cells

Cited by 20 publications

References 69 publications

DDI2 protease activity controls embryonic development and inflammation via TCF11/NRF1

DDI2 protease activity controls embryonic development and inflammation via TCF11/NRF1

The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress

The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

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