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. Author manuscript; available in PMC: 2011 Oct 7.
Published in final edited form as: Oncogene. 2010 Dec 6;30(14):1716–1726. doi: 10.1038/onc.2010.550

Figure 7. NS depletion triggers a compensatory up-regulation of GNL3L in HCT116 and U2OS cells.

Figure 7

(a1) qRT-PCR measurements revealed a compensatory up-regulation of GNL3L transcripts following NS knockdown in p53-wild-type and null HCT116 cells and U2OS cells but not in HeLa or HEK293 cells. Conversely, GNL3L knockdown shows no such effect on NS. (a2) The increase of GNL3L expression by NS knockdown was confirmed by western blots. (b) Mycophenolic acid (MPA) treatment triggers a reciprocal increase of GNL3L and decrease of NS in HCT116-8 and 2 cells. The MPA-induced GNL3L up-regulation can be reversed by MG132 treatment but not by NS overexpression. (c) GNL3L can functionally rescue the MDM2 ubiquitylation phenotype of NS-knockdown cells. (d) GNL3L and NS form a complex regulatory network on the MDM2-p53 pathway. Both proteins show similar activities in MDM2 stabilization but differ in their modes of regulation. Multiple points of feedback and cross-regulation exist. Arrows and X’s indicate excitatory or inhibitory functions, respectively, and the dashed line represents an event regulated by the nucleolar release mechanism.