TY - JOUR
T1 - Nucleolar stress
T2 - From development to cancer
AU - Lafita-Navarro, M. Carmen
AU - Conacci-Sorrell, Maralice
N1 - Funding Information:
The work was financially supported by American Cancer Society 724003 , Welch Foundation I-2058–20210327 , NCI R01CA245548 , UTSW Kidney Cancer SPORE Career Enhancement Program P50CA196516 to MCS, and a training fellowship supported by a Hamon Center for Regenerative Science and Medicine to MLN. MCS is the Virginia Murchison Linthicum Scholar in Medical Research. The authors acknowledge the UT Southwestern Live Cell Imaging Facility (Harold C. Simmons Cancer Center) supported in part by an NCI Cancer Center Support Grant, 1P30 CA142543-01 .
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022
Y1 - 2022
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
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
SN - 1084-9521
ER -