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Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence

López, Aida Rodríguez ; Jørgensen, Maria H. ; Havelund, Jesper F. ; Arendrup, Frederic S. ; Kolapalli, Srinivasa Prasad ; Nielsen, Thorbjørn M. ; Pais, Eva ; Beese, Carsten Jörn ; Abdul-Al, Ahmad and Vind, Anna Constance , et al. (2023) In Cell Reports 42(11). p.1-23
Abstract

Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the ribosome during the transition to OIS. This release of USP10 leads to an enhanced ribosome ubiquitination, particularly of small subunit proteins, including lysine 275 on RPS2. Both reinforcement of the USP10-ribosome interaction and mutation of... (More)

Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the ribosome during the transition to OIS. This release of USP10 leads to an enhanced ribosome ubiquitination, particularly of small subunit proteins, including lysine 275 on RPS2. Both reinforcement of the USP10-ribosome interaction and mutation of RPS2 K275 abrogate ribosomal delivery to lysosomes without affecting bulk autophagy. We show that the selective recruitment of ubiquitinated ribosomes to autophagosomes is mediated by the p62 receptor. While ribophagy is not required for the establishment of senescence per se, it contributes to senescence-related metabolome alterations and facilitates the senescence-associated secretory phenotype.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autophagy, CP: Cell biology, CP: Molecular biology, oncogene-induced senescence, ribosomes, selective autophagy, ubiquitin, USP10
in
Cell Reports
volume
42
issue
11
article number
113381
pages
1 - 23
publisher
Cell Press
external identifiers
  • pmid:37930887
  • scopus:85175818246
ISSN
2211-1247
DOI
10.1016/j.celrep.2023.113381
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Authors
id
1aed8b81-1d22-4944-a843-7ca553203cc7
date added to LUP
2023-11-19 08:28:57
date last changed
2024-04-16 15:09:49
@article{1aed8b81-1d22-4944-a843-7ca553203cc7,
  abstract     = {{<p>Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the ribosome during the transition to OIS. This release of USP10 leads to an enhanced ribosome ubiquitination, particularly of small subunit proteins, including lysine 275 on RPS2. Both reinforcement of the USP10-ribosome interaction and mutation of RPS2 K275 abrogate ribosomal delivery to lysosomes without affecting bulk autophagy. We show that the selective recruitment of ubiquitinated ribosomes to autophagosomes is mediated by the p62 receptor. While ribophagy is not required for the establishment of senescence per se, it contributes to senescence-related metabolome alterations and facilitates the senescence-associated secretory phenotype.</p>}},
  author       = {{López, Aida Rodríguez and Jørgensen, Maria H. and Havelund, Jesper F. and Arendrup, Frederic S. and Kolapalli, Srinivasa Prasad and Nielsen, Thorbjørn M. and Pais, Eva and Beese, Carsten Jörn and Abdul-Al, Ahmad and Vind, Anna Constance and Bartek, Jiri and Bekker-Jensen, Simon and Montes, Marta and Galanos, Panagiotis and Faergeman, Nils and Happonen, Lotta and Frankel, Lisa B.}},
  issn         = {{2211-1247}},
  keywords     = {{autophagy; CP: Cell biology; CP: Molecular biology; oncogene-induced senescence; ribosomes; selective autophagy; ubiquitin; USP10}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  pages        = {{1--23}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2023.113381}},
  doi          = {{10.1016/j.celrep.2023.113381}},
  volume       = {{42}},
  year         = {{2023}},
}