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. 2020 Jun 15;11:3018. doi: 10.1038/s41467-020-16589-8

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a Principal component analysis of transcriptomes of wild-type and Bap1-knockout cell lines established from the Pdx1^Cre;Kras^G12D cohort. b Canonical pathway (top) and upstream regulator (bottom) IPA of DEG (fold change > 1.5 and p < 0.05) in Bap1-knockout cell lines. The x axis corresponds to the raw binomial p-values. c Left: western blotting showing BAP1 levels in PANC1 transfected with sgBAP1 or non-targeting guide sequence. Right: principal component analysis of transcriptomes of PANC1-treated with sgBAP1 before and 3 days after exposure to 10 Gy of IR. d Left: Venn diagram showing the overlap of DEG (fold change > 1.5 and p < 0.01) identified in PANC1 cells for the indicated conditions compared with non-treated control cells. Right: IPA of DEG for each condition compared to control. The x axis corresponds to the raw binomial p-values. e Representative metaphase spreads of murine pancreatic cancer cell lines of the indicated genotypes from the Pdx1^Cre cohort. Bap1^KO;Kras^G12D cells show aneuploidy, chromosome shattering, and incompletely condensed chromosomes in the right panels. Right: table shows the number of metaphase nuclei with numerical and structural abnormalities. Results are representative from at least two independently established cell lines for each genotype. Black arrows point to chromosome fragments. f Representative metaphase spreads of murine pancreatic cell lines before and 3 days after exposure to 10 Gy of IR. Black and green arrows point to chromosome fragments and the absence of centromeres, respectively. g Representative metaphase spreads of HEK293T cells treated with sgBAP1 before and 3 days after exposure to 10 Gy of IR. Black arrows point to chromosome fragments. h HEK293T cells were transfected with Flag-tagged wild-type and the indicated truncated mutants of BARD1 (left). Cells expressing full-length (FL) BARD1 were also exposed to 10 Gy of IR (last lane). Nuclear extracts were immunoprecipitated with anti-Flag antibody and analyzed by western blotting for the indicated endogenous proteins. Right: schematic of the BRCA1, BARD1, and BAP1 proteins. UCH, ubiquitin carboxyl-terminal hydrolase; BRCT, BRCA1 C terminus; ANK, Ankyrin tandem repeats; HBM, HCF-1-binding domain. Not to scale.