Project description:We performed an RNA-Seq analysis comparing thymic lymphoma tissues from the p53-null(n=2) and ΔNp63Δ/Δ;p53-/- (n=3) or ΔNp73Δ/Δ;p53-/-(n=3). Mice at 10 weeks of age were injected with either Ad-mCherry or Ad-CRE-mCherry to delete ΔNp63/ΔNp73 in the thymic lmyphomas. We aimed to test by deleting the DNp63/DNp73 in these p53-deficient tumors will mediate tumor regression and analyze the expression profile of the genes Examination of thymic lymphoma tissues in 3 different genotypes (p53-/- vs ΔNp63Δ/Δ;p53-/- or ΔNp73Δ/Δ;p53-/-)
Project description:We performed a smallRNA-Seq analysis comparing thymic lymphoma tissues from the p53-null (n=4) and ΔNp63Δ/Δ;p53-/- (n=3). Mice at 10 weeks of age were injected with either Ad-mCherry or Ad-CRE-mCherry to delete ΔNp63 in the thymic lmyphomas. We aimed to test by deleting the ΔNp63 in these p53-deficient tumors will mediate tumor regression and analyze the expression profile of the small RNAs
Project description:We performed an RNA-Seq analysis comparing thymic lymphoma tissues from the p53-null(n=2) and ΔNp63Δ/Δ;p53-/- (n=3) or ΔNp73Δ/Δ;p53-/-(n=3). Mice at 10 weeks of age were injected with either Ad-mCherry or Ad-CRE-mCherry to delete ΔNp63/ΔNp73 in the thymic lmyphomas. We aimed to test by deleting the DNp63/DNp73 in these p53-deficient tumors will mediate tumor regression and analyze the expression profile of the genes
Project description:Receptor-interacting protein kinase 3 (RIPK3) is the primary regulator of necroptotic cell death. RIPK3 expression is often silenced in various cancer cells, which suggests that it may have tumor suppressor properties. However, the exact mechanism by which RIPK3 negatively regulates cancer development and progression remains unclear. This report indicates that RIPK3 acts as a potent regulator of homeostatic proliferation of CD4+CD8+ double-positive (DP) thymocytes. Abnormal proliferation of RIPK3-deficient DP thymocytes occurs independently of the well-known role for RIPK3 in necroptosis (upstream of MLKL activation), and is associated with an incidental thymic mass, likely thymic hyperplasia. In addition, Ripk3-null mice developed increased thymic tumor formation accompanied by reduced host survival in the context of a N-ethyl-N-nitrosourea (ENU)-induced tumor model. Moreover, RIPK3 deficiency in p53-null mice promoted thymic lymphoma development via upregulated ERK signaling, which correlated with markedly reduced survival rates. Mechanistically, lymphocyte-specific protein tyrosine kinase (LCK) activates RIPK3, which in turn leads to increases in the phosphatase activity of protein phosphatase 2 (PP2A), thereby suppressing hyper-activation of ERK in DP thymocytes. Overall, these findings suggest that a RIPK3-PP2A-ERK signaling axis regulates DP thymocyte homeostasis and may provide a potential therapeutic target to improve thymic lymphoma therapies.
Project description:RNA-sequencing was performed to gain insight into the mechanism responsible for the apoptosis and cell cycle arrest induced by loss of Mdm2 in p53-null cells. Following CreERT2-mediated deletion of Mdm2 in three p53-null cell types (T cell lymphoma, sarcoma, and fibroblasts), RNA-sequencing was performed. This high-throughput data revealed Mdm2 deletion in p53-null cells upregulated p53/p73 transcriptional target genes known to induce apoptosis and cell cycle arrest.
Project description:P53 mutation is closely associated with the occurrence and progression of colon cancer. In this project, we did crotonylomics sequencing by using human colon cancer homologous cell line pair-HCT116+/+(with wild type p53) and HCT116-/- (with null p53). Crotonylomics sequencing results showed that p53 deficiency regulated crotonylation of non-histone proteins.