Targeting the nucleolus as a therapeutic strategy in human disease

Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates ageing in mice

“…S2 ). These observations are consistent with decades of work, which have indicated that whereas P53 plays a role in the response to NS, this insult ultimately kills cells in a p53-independent manner that remains to be understood 16,17 .…”

“…As a consequence, perturbing nucleolar function can have a profound impact on cell fitness and/or viability. Correspondingly, abnormalities in nucleolar activity or structure, now collectively known as NS, have often been found in tissues from patients of several human diseases such as ribosomopathies, cancer or neurodegeneration 17 . Very recent work added brachyphalangy, polydactyly and tibial aplasia/hypoplasia syndrome (BPTAS), to the type of diseases associated to nucleolar dysfunction 39 .…”

“…In addition to inducing NS with external agents, nucleolar alterations have been frequently documented in human disease 17 . For instance, aberrations in nucleolar shape and number are associated to poor prognosis in several cancer types 18 , and mutations or altered expression of r-proteins are often found in cancer cells 19,20 .…”

UTP11 deficiency suppresses cancer development via nucleolar stress and ferroptosis

“…It was reported that UTP11 is expressed in neurons of hippocampus, while downregulation of UTP11 may be associated with Alzheimer's disease, although the molecular basis is unclear [ 57 ]. Our study implies a potential mechanism for the causative role of UTP11 in neurodegenerative diseases, as nucleolar alterations and p53-induced cell death have been associated with the etiology of these diseases [ 58 , 59 ]. Thus, our study reveals a novel mechanism for UTP11 in cancer and possibly non-cancer diseases through the regulation of ribosome biogenesis and p53 activity.…”

Silica-coated LiYF4:Yb3+, Tm3+ upconverting nanoparticles are non-toxic and activate minor stress responses in mammalian cells

“…35 Nucleoli assemble ribosomal subunits and function as stress sensors. [36][37][38][39] Impairments in cellular homeostasis affect the overall nucleolar organization and individual nucleolar proteins. 40,41 The transcription factor p53 is closely linked to nucleolar functions and a major indicator of stress.…”