Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice

Yangbo Yue, Stanley G. Leung, Yueyong Liu, Yurong Huang, Kirsten Grundt, Anne Carine Østvold, Kuang-Yu Jen, David Schild, Jian Hua Mao, Claudia Wiese

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo. Trp53+/- Nucks1+/- mice frequently succumbed to CD4- CD8- TLs harboring translocations involving Igh but not Tcra/d, indicating TLs in Trp53+/- Nucks1+/- mice mostly originated prior to the double positive stage and at earlier lineage than TLs in Trp53+/- mice. Monoclonal rearrangements at Tcrb were more prevalent in TLs from Trp53+/- Nucks1+/- mice, as was infiltration of primary TL cells to distant organs (liver, kidney and spleen). We propose that, in the context of Trp53 deficiency, wild type levels of Nucks1 are required to suppress radiation-induced TL, likely through the role of the NUCKS1 protein in the DNA damage response.

Original languageEnglish (US)
Pages (from-to)61874-61889
Number of pages16
JournalOncotarget
Volume7
Issue number38
DOIs
StatePublished - Jan 1 2016

Fingerprint

Radiation
Lymphoma
Loss of Heterozygosity
DNA Damage
Alleles
Thymus Neoplasms
Gene Dosage
Whole-Body Irradiation
Thymus Gland
Vertebrates
Proteins
Spleen
Kidney
Liver
Neoplasms

Keywords

  • Double-strand break repair
  • Ionizing radiation
  • NUCKS1
  • Thymic lymphoma
  • V(D)J recombination

ASJC Scopus subject areas

  • Oncology

Cite this

Yue, Y., Leung, S. G., Liu, Y., Huang, Y., Grundt, K., Østvold, A. C., ... Wiese, C. (2016). Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice. Oncotarget, 7(38), 61874-61889. https://doi.org/10.18632/oncotarget.11297

Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice. / Yue, Yangbo; Leung, Stanley G.; Liu, Yueyong; Huang, Yurong; Grundt, Kirsten; Østvold, Anne Carine; Jen, Kuang-Yu; Schild, David; Mao, Jian Hua; Wiese, Claudia.

In: Oncotarget, Vol. 7, No. 38, 01.01.2016, p. 61874-61889.

Research output: Contribution to journalArticle

Yue, Y, Leung, SG, Liu, Y, Huang, Y, Grundt, K, Østvold, AC, Jen, K-Y, Schild, D, Mao, JH & Wiese, C 2016, 'Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice', Oncotarget, vol. 7, no. 38, pp. 61874-61889. https://doi.org/10.18632/oncotarget.11297
Yue Y, Leung SG, Liu Y, Huang Y, Grundt K, Østvold AC et al. Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice. Oncotarget. 2016 Jan 1;7(38):61874-61889. https://doi.org/10.18632/oncotarget.11297
Yue, Yangbo ; Leung, Stanley G. ; Liu, Yueyong ; Huang, Yurong ; Grundt, Kirsten ; Østvold, Anne Carine ; Jen, Kuang-Yu ; Schild, David ; Mao, Jian Hua ; Wiese, Claudia. / Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice. In: Oncotarget. 2016 ; Vol. 7, No. 38. pp. 61874-61889.
@article{8ae1242a4a6147b8b8fea38aeb1e39a0,
title = "Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice",
abstract = "NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo. Trp53+/- Nucks1+/- mice frequently succumbed to CD4- CD8- TLs harboring translocations involving Igh but not Tcra/d, indicating TLs in Trp53+/- Nucks1+/- mice mostly originated prior to the double positive stage and at earlier lineage than TLs in Trp53+/- mice. Monoclonal rearrangements at Tcrb were more prevalent in TLs from Trp53+/- Nucks1+/- mice, as was infiltration of primary TL cells to distant organs (liver, kidney and spleen). We propose that, in the context of Trp53 deficiency, wild type levels of Nucks1 are required to suppress radiation-induced TL, likely through the role of the NUCKS1 protein in the DNA damage response.",
keywords = "Double-strand break repair, Ionizing radiation, NUCKS1, Thymic lymphoma, V(D)J recombination",
author = "Yangbo Yue and Leung, {Stanley G.} and Yueyong Liu and Yurong Huang and Kirsten Grundt and {\O}stvold, {Anne Carine} and Kuang-Yu Jen and David Schild and Mao, {Jian Hua} and Claudia Wiese",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.11297",
language = "English (US)",
volume = "7",
pages = "61874--61889",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "38",

}

TY - JOUR

T1 - Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice

AU - Yue, Yangbo

AU - Leung, Stanley G.

AU - Liu, Yueyong

AU - Huang, Yurong

AU - Grundt, Kirsten

AU - Østvold, Anne Carine

AU - Jen, Kuang-Yu

AU - Schild, David

AU - Mao, Jian Hua

AU - Wiese, Claudia

PY - 2016/1/1

Y1 - 2016/1/1

N2 - NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo. Trp53+/- Nucks1+/- mice frequently succumbed to CD4- CD8- TLs harboring translocations involving Igh but not Tcra/d, indicating TLs in Trp53+/- Nucks1+/- mice mostly originated prior to the double positive stage and at earlier lineage than TLs in Trp53+/- mice. Monoclonal rearrangements at Tcrb were more prevalent in TLs from Trp53+/- Nucks1+/- mice, as was infiltration of primary TL cells to distant organs (liver, kidney and spleen). We propose that, in the context of Trp53 deficiency, wild type levels of Nucks1 are required to suppress radiation-induced TL, likely through the role of the NUCKS1 protein in the DNA damage response.

AB - NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo. Trp53+/- Nucks1+/- mice frequently succumbed to CD4- CD8- TLs harboring translocations involving Igh but not Tcra/d, indicating TLs in Trp53+/- Nucks1+/- mice mostly originated prior to the double positive stage and at earlier lineage than TLs in Trp53+/- mice. Monoclonal rearrangements at Tcrb were more prevalent in TLs from Trp53+/- Nucks1+/- mice, as was infiltration of primary TL cells to distant organs (liver, kidney and spleen). We propose that, in the context of Trp53 deficiency, wild type levels of Nucks1 are required to suppress radiation-induced TL, likely through the role of the NUCKS1 protein in the DNA damage response.

KW - Double-strand break repair

KW - Ionizing radiation

KW - NUCKS1

KW - Thymic lymphoma

KW - V(D)J recombination

UR - http://www.scopus.com/inward/record.url?scp=84991758890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991758890&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.11297

DO - 10.18632/oncotarget.11297

M3 - Article

C2 - 27542204

AN - SCOPUS:84991758890

VL - 7

SP - 61874

EP - 61889

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 38

ER -