1. Sollner-Webb B, Tower J. Transcription of cloned eukaryotic ribosomal RNA genes. Annu Rev Biochem. 1986;55:801-830.
2. Schmidt EV. The role of c-myc in cellular growth control. Oncogene.
1999;18:2988-2996.
3. Yang K, Yang J, Yi J. Nucleolar stress: hallmarks, sensing mechanism
and diseases. Cell Stress. 2018;2:125-140.
4. Lindstrom MS, Bartek J, Maya-Mendoza A. p53 at the crossroad
of DNA replication and ribosome biogenesis stress pathways. Cell
Death Differ. 2022;29:972-982.
5. Matthews DA. Adenovirus protein V induces redistribution
of nucleolin and B23 from nucleolus to cytoplasm. J Virol.
2001;75:1031-1038.
6. Westdorp KN, Sand A, Moorman NJ, Terhune SS. Cytomegalovirus
late protein pUL31 alters pre-rRNA expression and nuclear organization during infection. J Virol. 2017;91:e00593-17.
7. Poortinga G, Hannan KM, Snelling H, et al. MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J. 2004;23:3325-3335.
8. Grandori C, Gomez-Roman N, Felton-Edkins ZA, et al. c-Myc binds
to human ribosomal DNA and stimulates transcription of rRNA
genes by RNA polymerase I. Nat Cell Biol. 2005;7:311-318.
9. Arabi A, Wu S, Ridderstrale K, et al. c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell
Biol. 2005;7:303-310.
10. Zhao J, Yuan X, Frodin M, Grummt I. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required
for RNA polymerase I transcription and cell growth. Mol Cell.
2003;11:405-413.
11. Chan JC, Hannan KM, Riddell K, et al. AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome biogenesis in
cancer. Sci Signal. 2011;4:ra56.
12. Perry RP, Kelley DE. Inhibition of RNA synthesis by actinomycin
D: characteristic dose-response of different RNA species. J Cell
Physiol. 1970;76:127-139.
13. Burger K, Muhl B, Harasim T, et al. Chemotherapeutic drugs
inhibit ribosome biogenesis at various levels. J Biol Chem.
2010;285:12416-12425.
14. Rubbi CP, Milner J. Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses. EMBO
J. 2003;22:6068-6077.
15. Holzel M, Orban M, Hochstatter J, et al. Defects in 18S or
28S rRNA processing activate the p53 pathway. J Biol Chem.
2010;285:6364-6370.
16. Russo A, Russo G. Ribosomal proteins control or bypass p53 during
nucleolar stress. Int J Mol Sci. 2017;18:140.
17. Luan Y, Tang N, Yang J, et al. Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human
cells. Nucleic Acids Res. 2022;50:6601-6617.
18. James A, Wang Y, Raje H, Rosby R, DiMario P. Nucleolar stress with
and without p53. Nucleus. 2014;5:402-426.
19. Sloan KE, Bohnsack MT, Watkins NJ. The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress. Cell Rep.
2013;5:237-247.
20. Sasaki M, Kawahara K, Nishio M, et al. Regulation of the MDM2-P53
pathway and tumor growth by PICT1 via nucleolar RPL11. Nat Med.
2011;17:944-951.
21. Suzuki A, Kogo R, Kawahara K, et al. A new PICTure of nucleolar
stress. Cancer Sci. 2012;103:632-637.
22. Ichikawa MK, Saitoh M. Direct and indirect roles of GRWD1 in the
inactivation of p53 in cancer. J Biochem. 2022;171:601-603.
23. Kuroda T, Murayama A, Katagiri N, et al. RNA content in
the nucleolus alters p53 acetylation via MYBBP1A. EMBO J.
2011;30:1054-1066.
24. Gjerset RA, Bandyopadhyay K. Regulation of p14ARF through subnuclear compartmentalization. Cell Cycle. 2006;5:686-690.
25. Anderson SJ, Lauritsen JP, Hartman MG, et al. Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity.
2007;26:759-772.
26. Takagi M, Absalon MJ, McLure KG, Kastan MB. Regulation of p53
translation and induction after DNA damage by ribosomal protein
L26 and nucleolin. Cell. 2005;123:49-63.
13497006, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cas.15755 by Kobe University, Wiley Online Library on [08/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2084 27. Wang HT, Chen TY, Weng CW, Yang CH, Tang MS. Acrolein preferentially damages nucleolus eliciting ribosomal stress and apoptosis
in human cancer cells. Oncotarget. 2016;7:80450-8 0464.
28. Donati G, Montanaro L, Derenzini M. Ribosome biogenesis
and control of cell proliferation: p53 is not alone. Cancer Res.
2012;72:1602-1607.
29. Challagundla KB, Sun XX, Zhang X, et al. Ribosomal protein L11
recruits miR-24/miRISC to repress c-Myc expression in response to
ribosomal stress. Mol Cell Biol. 2011;31:4007-4 021.
3 0. van Riggelen J, Yetil A, Felsher DW. MYC as a regulator of ribosome
biogenesis and protein synthesis. Nat Rev Cancer. 2010;10:301-3 09.
31. Russo A, Esposito D, Catillo M, Pietropaolo C, Crescenzi E, Russo
G. Human rpL3 induces G(1)/S arrest or apoptosis by modulating
p21 (waf1/cip1) levels in a p53-independent manner. Cell Cycle.
2013;12:76-87.
32. Pagliara V, Saide A, Mitidieri E, et al. 5-FU targets rpL3 to induce
mitochondrial apoptosis via cystathionine-beta-synthase in colon
cancer cells lacking p53. Oncotarget. 2016;7:50333-50348.
33. Chen J, Stark LA. Insights into the relationship between nucleolar
stress and the NF-kappaB pathway. Trends Genet. 2019;35:768-780.
3 4. Pfister AS, Keil M, Kuhl M. The Wnt target protein Peter pan defines a novel p53-independent nucleolar stress-response pathway.
J Biol Chem. 2015;290:10905-10918.
35. Lafita-Navarro MC, Conacci-Sorrell M. Nucleolar stress: from development to cancer. Semin Cell Dev Biol. 2022;136:64-74.
36. Sulima SO, Kampen KR, De Keersmaecker K. Cancer biogenesis in
Ribosomopathies. Cells. 2019;8:229.
37. McGowan KA, Mason PJ. Animal models of diamond Blackfan anemia. Semin Hematol. 2011;48:106-116.
38. Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q-syndrome gene by RNA interference screen. Nature. 2008;451:335-339.
39. Boocock GR, Morrison JA, Popovic M, et al. Mutations in SBDS
are associated with Shwachman-diamond syndrome. Nat Genet.
2003;33:97-101.
4 0. Hao Q, Wang J, Chen Y, et al. Dual regulation of p53 by the ribosome maturation factor SBDS. Cell Death Dis. 2020;11:197.
41. Gal Z, Nieto B, Boukoura S, Rasmussen AV, Larsen DH. Treacle
sticks the nucleolar responses to DNA damage together. Front Cell
Dev Biol. 2022;10:892006.
42. Armistead J, Khatkar S, Meyer B, et al. Mutation of a gene essential
for ribosome biogenesis, EMG1, causes Bowen-Conradi syndrome.
Am J Hum Genet. 2009;84:728-739.
43. Slomnicki LP, Chung DH, Parker A, Hermann T, Boyd NL, Hetman
M. Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the zika virus. Sci Rep. 2017;7:16652.
4 4. Zhang W, Cheng W, Parlato R, et al. Nucleolar stress induces a
senescence-like phenotype in smooth muscle cells and promotes development of vascular degeneration. Aging. 2020;12:22174-22198.
45. Weishaupt JH, Hyman T, Dikic I. Common molecular pathways in
amyotrophic lateral sclerosis and frontotemporal dementia. Trends
Mol Med. 2016;22:769-783.
46. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, et al. Expanded
GGGGCC hexanucleotide repeat in noncoding region of
C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron.
2011;72:245-256.
47. Tao Z, Wang H, Xia Q, et al. Nucleolar stress and impaired stress
granule formation contribute to C9orf72 RAN translation-induced
cytotoxicity. Hum Mol Genet. 2015;24:2426-2441.
48. Tsoi H, Lau TC, Tsang SY, Lau KF, Chan HY. CAG expansion induces
nucleolar stress in polyglutamine diseases. Proc Natl Acad Sci U S A.
2012;109:13428-13433.
49. Kang H, Shin JH. Repression of rRNA transcription by PARIS contributes to Parkinson's disease. Neurobiol Dis. 2015;73:220-228.
2085
50. Kofuji S, Hirayama A, Eberhardt AO, et al. IMP dehydrogenase-2
drives aberrant nucleolar activity and promotes tumorigenesis in
glioblastoma. Nat Cell Biol. 2019;21:1003-1014.
51. Lafita-Navarro MC, Venkateswaran N, Kilgore JA, et al. Inhibition
of the de novo pyrimidine biosynthesis pathway limits ribosomal
RNA transcription causing nucleolar stress in glioblastoma cells.
PLoS Genet. 2020;16:e1009117.
52. Hubackova S, Davidova E, Boukalova S, et al. Replication and ribosomal stress induced by targeting pyrimidine synthesis and cellular checkpoints suppress p53-deficient tumors. Cell Death Dis.
2020;11:110.
53. De Keersmaecker K, Atak ZK, Li N, et al. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in
T-cell acute lymphoblastic leukemia. Nat Genet. 2013;45:186-190.
54. Sulima SO, Hofman IJF, De Keersmaecker K, Dinman JD. How ribosomes translate cancer. Cancer Discov. 2017;7:1069-1087.
55. Sulima SO, Patchett S, Advani VM, De Keersmaecker K, Johnson
AW, Dinman JD. Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis. Proc Natl Acad Sci U S A.
2014;111:5640-5645.
56. Paolini NA, Attwood M, Sondalle SB, et al. A Ribosomopathy reveals decoding defective ribosomes driving human dysmorphism.
Am J Hum Genet. 2017;100:506-522.
57. Kampen KR, Sulima SO, Verbelen B, et al. The ribosomal RPL10
R98S mutation drives IRES-dependent BCL-2 translation in T-ALL.
Leukemia. 2019;33:319-332.
58. Bellodi C, Kopmar N, Ruggero D. Deregulation of oncogene-
induced senescence and p53 translational control in X-linked dyskeratosis congenita. EMBO J. 2010;29:1865-1876.
59. Yoon A, Peng G, Brandenburger Y, et al. Impaired control of IRES-
mediated translation in X-linked dyskeratosis congenita. Science.
2006;312:902-906.
60. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24:R453-R462.
61. Ishikawa K, Takenaga K, Akimoto M, et al. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis.
Science. 2008;320:661-664.
62. Woo DK, Green PD, Santos JH, et al. Mitochondrial genome instability and ROS enhance intestinal tumorigenesis in APC(min/+)
mice. Am J Pathol. 2012;180:24-31.
63. Ravera S, Dufour C, Cesaro S, et al. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-
diamond syndrome. Sci Rep. 2016;6:25441.
6 4. Zambetti NA, Ping Z, Chen S, et al. Mesenchymal inflammation
drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell.
2016;19:613-627.
65. Kapralova K, Jahoda O, Koralkova P, et al. Oxidative DNA damage,
inflammatory signature, and altered erythrocytes properties in
diamond-Blackfan anemia. Int J Mol Sci. 2020;21:9652.
66. Ferreira R, Schneekloth JS Jr, Panov KI, Hannan KM, Hannan RD.
Targeting the RNA polymerase I transcription for cancer therapy
comes of age. Cell. 2020;9:226.
67. Xu H, Di Antonio M, McKinney S, et al. CX-5461 is a DNA G-
quadruplex stabilizer with selective lethality in BRCA1/2 deficient
tumours. Nat Commun. 2017;8:14432.
68. Jacobs RQ, Huffines AK, Laiho M, Schneider DA. The small-
molecule BMH-21 directly inhibits transcription elongation and
DNA occupancy of RNA polymerase I in vivo and in vitro. J Biol
Chem. 2022;298:101450.
69. Colis L, Peltonen K, Sirajuddin P, et al. DNA intercalator BMH-21
inhibits RNA polymerase I independent of DNA damage response.
Oncotarget. 2014;5:4361-4369.
13497006, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cas.15755 by Kobe University, Wiley Online Library on [08/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MAEHAMA et al.
70. Huang M, Ji Y, Itahana K, Zhang Y, Mitchell B. Guanine nucleotide
depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption. Leuk Res. 2008;32:131-141.
71. Tafforeau L, Zorbas C, Langhendries JL, et al. The complexity of human ribosome biogenesis revealed by systematic nucleolar screening of pre-rRNA processing factors. Mol Cell.
2013;51:539-551.
MAEHAMA et al.
How to cite this article: Maehama T, Nishio M, Otani J, Mak
TW, Suzuki A. Nucleolar stress: Molecular mechanisms and
related human diseases. Cancer Sci. 2023;114:2078-2086.
doi:10.1111/cas.15755
13497006, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cas.15755 by Kobe University, Wiley Online Library on [08/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2086 ...