Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence

Asimina Pantazi, Andrea Quintanilla, Priya Hari, Nuria Tarrats, Eleftheria Parasyraki, Flora L. Dix, Jaiyogesh Patel, Tamir Chandra, Juan Carlos Acosta, Andrew J. Finch

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Cellular senescence is triggered by diverse stimuli and is characterised by long-term growth arrest and secretion of cytokines and chemokines (termed the SASP - senescence-associated secretory phenotype). Senescence can be organismally
beneficial as it can prevent the propagation of damaged or mutated clones and
stimulate their clearance by immune cells. However, it has recently become clear that senescence also contributes to the pathophysiology of aging through the accumulation of damaged cells within tissues. Here we describe that inhibition of the reaction catalysed by LSG1, a GTPase involved in the biogenesis of the 60S ribosomal subunit, leads to a robust induction of cellular senescence. Perhaps surprisingly, this was not due to ribosome depletion or translational insufficiency, but rather through perturbation of endoplasmic reticulum (ER) homeostasis and a dramatic upregulation of the cholesterol biosynthesis pathway. The underlying transcriptomic signature is shared with several other forms of senescence and the cholesterol biosynthesis genes contribute to the cell cycle arrest in oncogene-induced senescence (OIS). Furthermore, targetting of LSG1 resulted in amplification of the cholesterol/ER signature and restoration of a robust cellular senescence response
Original languageEnglish
JournalAging Cell
Publication statusPublished - 31 May 2019

Keywords / Materials (for Non-textual outputs)

  • cellular senescence
  • cholesterol biosynthesis
  • ribosome biogenesis
  • SASP
  • ER
  • Tumour Suppression


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