prikaz prve stranice dokumenta Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint
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Scientific paper - Original scientific paper
Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint
Oncogene, 39 (2020), 17; 344-357. https://doi.org/10.1038/s41388-020-1231-6
Oršolić, Ines; Bursać, Slađana; Jurada, Deana; Drmić Hofman, Irena; Dembić, Zlatko; Bartek, Jiri; Mihalek, Ivana; Volarević, Siniša

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Oršolić, I., Bursać, S., Jurada, D., Drmić Hofman, I., Dembić, Z., Bartek, J. ... Volarević, S. (2020). Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint. Oncogene, 39. (17), 344-357. doi: 10.1038/s41388-020-1231-6

Oršolić, Ines, et al. "Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint." Oncogene, vol. 39, no. 17, 2020, pp. 344-357. https://doi.org/10.1038/s41388-020-1231-6

Oršolić, Ines, Slađana Bursać, Deana Jurada, Irena Drmić Hofman, Zlatko Dembić, Jiri Bartek, Ivana Mihalek and Siniša Volarević. "Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint." Oncogene 39, no. 17 (2020): 344-357. https://doi.org/10.1038/s41388-020-1231-6

Oršolić, I., et al. (2020) 'Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint', Oncogene, 39(17), pp. 344-357. doi: 10.1038/s41388-020-1231-6

Oršolić I, Bursać S, Jurada D, Drmić Hofman I, Dembić Z, Bartek J, and sur.. Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint. Oncogene [Internet]. 2020 February 27 [cited 2024 November 23];39(17):344-357. doi: 10.1038/s41388-020-1231-6

I. Oršolić, et al., "Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint", Oncogene, vol. 39, no. 17, pp. 344-357, February 2020. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:956160. [Accessed: 23 November 2024]

Metadata
Title (english)Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint
AuthorInes Oršolić
AuthorSlađana Bursać
AuthorDeana Jurada
AuthorIrena Drmić Hofman
AuthorZlatko Dembić
AuthorJiri Bartek
AuthorIvana Mihalek
AuthorSiniša Volarević
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of Molecular Medicine and Biotechnology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract (english)
Perturbations in ribosome biogenesis have been associated with cancer. Such aberrations activate p53 through the RPL5/RPL11/5S rRNA complex-mediated inhibition of HDM2. Studies using animal models have suggested that this signaling pathway might constitute an important anticancer barrier. To gain a deeper insight into this issue in humans, here we analyze somatic mutations in RPL5 and RPL11 coding regions, reported in The Cancer Genome Atlas and International Cancer Genome Consortium databases. Using a combined computational and statistical approach, complemented by a range of biochemical and functional analyses in human cancer cell models, we demonstrate the existence of several mechanisms by which RPL5 mutations may impair wild-type p53 upregulation and ribosome biogenesis. Unexpectedly, the same approach provides only modest evidence for a similar role of RPL11, suggesting that RPL5 represents a preferred target during human tumorigenesis in cancers with wild-type p53. Furthermore, we find that several functional cancer-associated RPL5 somatic mutations occur as rare germline variants in general population. Our results shed light on the so-far enigmatic role of cancer-associated mutations in genes encoding ribosomal proteins, with implications for our understanding of the tumor suppressive role of the RPL5/RPL11/5S rRNA complex in human malignancies.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titleOncogene
Numberingvol. 39, no. 17, pp. 344-357
p-ISSN0950-9232
e-ISSN1476-5594
DOIhttps://doi.org/10.1038/s41388-020-1231-6
URN:NBNurn:nbn:hr:184:956160
Online first2020-02-27
ProjectNumber: 09.01/220
Title (croatian): Uloga ribosomskih proteina L5 i L11 u aktivaciji tumor supresora p53 i patogenezi zloćudnih tumora
Leader: Siniša Volarević
Jurisdiction: Croatia
Funding stream: IS
ProjectNumber: IP-2016-06-2079
Title (croatian): Uloga heterozigotnosti gena za ribosomski protein S6 u zloćudnoj preoprazbi stanica
Acronym: ONCO-RIB
Leader: Siniša Volarević
Jurisdiction: Croatia
Funding stream: IP
Document URLhttp://www.nature.com/articles/s41388-020-1231-6
Type of resourceText
Access conditionsRestricted access
Terms of useLicence In copyright icon
Created on2020-03-10 08:46:32