Senescent cells form nuclear foci that contain the 26S proteasome

Iriki, Tomohiro; Iio, Hiroyuki; Yasuda, Shu; Masuta, Shun; Kato, Masakazu; Kosako, Hidetaka; Hirayama, Shoshiro; Endo, Akinori; Ohtake, Fumiaki; Kamiya, Mako; Urano, Yasuteru; Saeki, Yasushi; Hamazaki, Jun; Murata, Shigeo

doi:10.1016/j.celrep.2023.112880

Cited by 3 publications

(3 citation statements)

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“…However, unlike the previous proteasome foci, proteasome activity was also required for SANPs formation. Inhibiting the formation of SANPs enhanced mitochondrial activity, suggesting the pivotal role of SANPs in regulating mitochondrial function in senescent cells, possibly by degrading some nuclear proteins in senescent cells ( 28 ) .…”

Section: The Proteasome and Cellular Senescencementioning

confidence: 99%

Relationships between protein degradation, cellular senescence, and organismal aging

Hamazaki,

Murata

2024

The Journal of Biochemistry

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Summary Aging is a major risk factor for many diseases. Recent studies have shown that age-related disruption of proteostasis leads to the accumulation of abnormal proteins and that dysfunction of the two major intracellular proteolytic pathways, the ubiquitin-proteasome pathway, and the autophagy-lysosome pathway, is largely responsible for this process. Conversely, it has been shown that activation of these proteolytic pathways may contribute to lifespan extension and suppression of pathological conditions, making it a promising intervention for anti-aging. This review provides an overview of the important role of intracellular protein degradation in aging and summarizes how the disruption of proteostasis is involved in age-related diseases.

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Section: The Proteasome and Cellular Senescencementioning

confidence: 99%

Relationships between protein degradation, cellular senescence, and organismal aging

Hamazaki,

Murata

2024

The Journal of Biochemistry

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“…[25] [ However, a recent study has discovered that senescent cells have increased formation of nuclear foci that contain an increased amount of 26S proteasome .32] It is suggested that the formation of senescence-associated nuclear proteasome foci (SANPs) play an important role in senescent cell maintenance and health. [32] This study observed the effects of inhibiting the formation of SANPs. [33] They observed a significant increase in ROS production when SANPs formation was inhibited through RAD23B knockdown.…”

Section: Attenuation Of Senescence and Proteasome Activity Impairmentmentioning

confidence: 99%

“…[15,16] Impairment of the proteasome activity has also been indicated in these diseases. [32,[37][38][39] The misfolded protein that is linked to PD is α-synuclein. The proteasome can degrade α-synuclein through both ubiquitin-dependent and -independent pathways.…”

Section: Misfolded Proteins and Age-related Neurodegenerative Diseasesmentioning

confidence: 99%

The Role of the Proteasome in Limiting Cellular Stress Associated with Protein Accumulation

Kragness,

Trader

2023

Israel Journal of Chemistry

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The proteasome is comprised of multiple subunits that catalyze the degradation of proteins to maintain cellular homeostasis. The proteasome targets protein substrates by two different pathways. The ubiquitin‐dependent pathway requires proteins to be labeled with a ubiquitin tag to signal for degradation by the 26S isoform of the proteasome. Protein degradation through this pathway declines during age progression. The ubiquitin‐independent pathway utilizes the 20S proteasome isoform. It can degrade misfolded and intrinsically disordered proteins to decrease cellular stress. Age‐related protein accumulation and aggregation can occur due to the decreased activity and expression of the proteasome. Protein accumulation causes increased cellular stress which can contribute to disease progression. Increasing proteasome activity could serve as a solution to eliminating and preventing protein accumulation. Studies have shown the value of the proteasome as a therapeutic entity to mitigate cellular stress. This perspective explores the link between proteasome activity and cellular stress caused by age‐related misfolded protein accumulation.

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