TY - JOUR
T1 - Nucleolar stress
T2 - From development to cancer
AU - Lafita-Navarro, M. Carmen
AU - Conacci-Sorrell, Maralice
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2023/2/28
Y1 - 2023/2/28
N2 - The nucleolus is a large nuclear membraneless organelle responsible for ribosome biogenesis. Ribosomes are cytoplasmic macromolecular complexes comprising RNA and proteins that link amino acids together to form new proteins. The biogenesis of ribosomes is an intricate multistep process that involves the transcription of ribosomal DNA (rDNA), the processing of ribosomal RNA (rRNA), and the assembly of rRNA with ribosomal proteins to form active ribosomes. Nearly all steps necessary for ribosome production and maturation occur in the nucleolus. Nucleolar shape, size, and number are directly linked to ribosome biogenesis. Errors in the steps of ribosomal biogenesis are sensed by the nucleolus causing global alterations in nucleolar function and morphology. This phenomenon, known as nucleolar stress, can lead to molecular changes such as stabilization of p53, which in turn activates cell cycle arrest or apoptosis. In this review, we discuss recent work on the association of nucleolar stress with degenerative diseases and developmental defects. In addition, we highlight the importance of de novo nucleotide biosynthesis for the enhanced nucleolar activity of cancer cells and discuss targeting nucleotide biosynthesis as a strategy to activate nucleolar stress to specifically target cancer cells.
AB - The nucleolus is a large nuclear membraneless organelle responsible for ribosome biogenesis. Ribosomes are cytoplasmic macromolecular complexes comprising RNA and proteins that link amino acids together to form new proteins. The biogenesis of ribosomes is an intricate multistep process that involves the transcription of ribosomal DNA (rDNA), the processing of ribosomal RNA (rRNA), and the assembly of rRNA with ribosomal proteins to form active ribosomes. Nearly all steps necessary for ribosome production and maturation occur in the nucleolus. Nucleolar shape, size, and number are directly linked to ribosome biogenesis. Errors in the steps of ribosomal biogenesis are sensed by the nucleolus causing global alterations in nucleolar function and morphology. This phenomenon, known as nucleolar stress, can lead to molecular changes such as stabilization of p53, which in turn activates cell cycle arrest or apoptosis. In this review, we discuss recent work on the association of nucleolar stress with degenerative diseases and developmental defects. In addition, we highlight the importance of de novo nucleotide biosynthesis for the enhanced nucleolar activity of cancer cells and discuss targeting nucleotide biosynthesis as a strategy to activate nucleolar stress to specifically target cancer cells.
KW - Nucleolar stress
KW - Nucleolus
KW - Nucleotides
KW - Ribosome biogenesis
KW - Ribosomopathies
KW - rRNA
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U2 - 10.1016/j.semcdb.2022.04.001
DO - 10.1016/j.semcdb.2022.04.001
M3 - Review article
C2 - 35410715
AN - SCOPUS:85127804721
SN - 1084-9521
VL - 136
SP - 64
EP - 74
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
ER -