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

doi:10.18632/oncotarget.11297

Title: Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice

Journal Article · Tue Aug 16 00:00:00 EDT 2016 · Oncotarget

DOI:https://doi.org/10.18632/oncotarget.11297· OSTI ID:1378756

Yue, Yangbo ^[1]; Leung, Stanley G. ^[1]; Liu, Yueyong ^[1]; Huang, Yurong ^[1]; Grundt, Kirsten ^[2]; Østvold, Anne-Carine ^[2]; Jen, Kuang-Yu ^[3]; Schild, David ^[1]; Mao, Jian-Hua ^[1]; Wiese, Claudia ^[4]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Department of Organismal Systems and Bioresilience, Biological Systems and Engineering Division
Univ. of Oslo (Norway). Department of Molecular Medicine, Institute of Basic Medical Science
Univ. of California, Davis, CA (United States). Department of Pathology and Laboratory Medicine
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Department of Organismal Systems and Bioresilience, Biological Systems and Engineering Division; Colorado State Univ., Fort Collins, CO (United States). Department of Environmental and Radiological Health Sciences

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1378756

Journal Information:: Oncotarget, Vol. 7, Issue 38; ISSN 1949-2553

Publisher:: Impact JournalsCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 7 works

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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
NUCKS1
double-strand break repair
ionizing radiation
thymic lymphoma
V(D)J recombination

Title: Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice

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