Figure 6: CSN6 haplo-insufficiency delays the onset/progression of Myc-mediated lymphomagenesis.
From: CSN6 drives carcinogenesis by positively regulating Myc stability
(a) Survival of Eμ-Myc mice was prolonged by CSN6 haplo-insufficiency. The genotypes of the transgenic mice are indicated next to the Kaplan–Meier survival curves. The numbers of mice analysed in each group are denoted. (b) CSN6 haplo-insufficiency caused low levels of Cullin neddylation and low expression of Myc. Lymphoma tissues from Eμ-Myc/Csn6+/+ (1–10) and Eμ-Myc/Csn6+/− (11–25) mice were immunoblotted with the indicated antibodies. (c) Levels of Fbxw7 were elevated in lymphomas from Eμ-Myc/Csn6+/− mice. Lymphomas arising from mice from b underwent IHC staining. Representative photographs of Fbxw7 and haematoxylin and eosin staining are shown. Scale bar: 50μm. (d) Levels of neddylated Cullin and Myc were reduced and level of Fbxw7 was increased in lymphomas from transgenic mice. Levels of indicated proteins in lymphomas arising from mice in b and c were quantitated by integrating optical density from Image J and are demonstrated as bar graphs. Each result shown is representative of three independent experiments. Error bars represent 95% CI; Student’s t-test, *P<0.001. (e) The model depicts the pivotal role of the CSN6–Cullin–Fbxw7 axis in Myc-induced lymphomagenesis.
