Regulation of nucleolar signalling to p53 through NEDDylation of L11.
Several studies have shown that ribosomal proteins (RPs) are important mediators of p53 activation in response to nucleolar disruption; however, the pathways that control this signalling function of RPs are currently unknown. We have recently shown that RPs are targets for the ubiquitin-like molecule NEDD8, and that NEDDylation protects RPs from destabilization. Here, we identify NEDD8 as a crucial regulator of L11 RP signalling to p53. A decrease in L11 NEDDylation during nucleolar stress causes relocalization of L11 from the nucleolus to the nucleoplasm. This not only provides the signal for p53 activation, but also makes L11 susceptible to degradation. Mouse double minute 2 (MDM2) -mediated NEDDylation protects L11 from degradation and this is required for p53 stabilization during nucleolar stress. By controlling the correct localization and stability of L11, NEDD8 acts as a crucial, new regulator of nucleolar signalling to p53.
Sundqvist
Anders
A
Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Liu
Geng
G
Mirsaliotis
Antonis
A
Xirodimas
Dimitris P
DP
D021581:Active Transport, Cell Nucleus; D000818:Animals; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D000075687:NEDD8 Protein; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; C027624:ribosomal protein L11; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2