The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function

Koltowska, Katarzyna; Okuda, Kazuhide S.; Gloger, Marleen; Rondon‐Galeano, Maria; Mason, Elizabeth A.; Xuan, Jiachen; Dudczig, Stefanie; Chen, Huijun; Arnold, Hannah; Skoczylas, Renae; Bower, Neil I.; Paterson, Scott; Lagendijk, Anne K; Baillie, Gregory J.; Leshchiner, Ignaty; Simons, Cas; Smith, Kelly; Goessling, Wolfram; Heath, Joan K.; Pearson, Richard B.; Sanij, Elaine; Schulte‐Merker, Stefan; Hogan, Benjamin M.

doi:10.1038/s41556-021-00784-w

Cited by 33 publications

(16 citation statements)

References 72 publications

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“…Katarzyna and colleagues found that the RNA helicase Ddx21, an important regulator of rRNA synthesis and ribosome biogenesis, controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial ribosome biosynthesis and p53 function. 259 This mechanism may be targeted in diseases of hyperlymphangiogenesis, such as cancer metastasis or lymphatic malformations. Fibrillin (FBL), a ribosomal biogenic factor, plays an important role in the early steps of ribosome biogenesis and is associated with poor prognosis in breast cancer when overexpressed.…”

Section: Ribosomes and Cancermentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

103

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The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

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Section: Ribosomes and Cancermentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

103

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“…Prox1 and GFP were detected by immunofluorescence staining as previously described (Le Guen et al, 2014;Shin et al, 2016), with the addition of a 25 min Proteinase K treatment at RT as described in (Koltowska et al, 2015b). To view 5-ethynyl-2 0 -deoxyuridine (EdU) incorporation into newly synthesised DNA we followed the method previously described in (Koltowska et al, 2021), with the adaptation that embryos were treated in EdU at 54 hpf and fixed at 56 hpf. Tg uu1kk staining was carried out using the method described above.…”

Section: Immunostainingmentioning

confidence: 99%

mafba and mafbb differentially regulate lymphatic endothelial cell migration in topographically distinct manners

Arnold

Panara

Hußmann³

et al. 2022

Cell Reports

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“…In our data, we observed that elevated LRRC59 expression was significantly associated with a positive nodal status, but the underlying mechanisms underpinning lymph node (LN) metastasis remain unexplored. Recent studies have shown that stress-related RNA helicase protein Ddx21 [28] , metabolic pathway regulatory factors YAP/TAZ [29] , and specific immune environment in LN might facilitate tumor colonization and metastasis [30] . We found that LRRC59 is significantly correlated with multiple stress-related genes in TCGA-BLCA data including DDX21 (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%