The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis
Authors: Anne Dejean
Klaus Schwamborn
Nadine Martin
Rudolf Grosschedl
Andreas Werner
Oliver Bischof
Claudio Sustmann
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cellular senescence; apoptosis; E3 SUMO ligase; PIASy; p53
Affiliations: Nuclear Organisation and Oncogenesis Unit, INSERM U579, Institut Pasteur, 75724 Paris Cedex 15, France.

Abstract:  Cellular senescence and apoptosis have evolved to restrain unwarranted proliferation of potentially tumorigenic cells. Here we show that overexpression of the E3 SUMO ligase PIASy in normal human fibroblasts recruits the p53 and Rb tumor suppressor pathways to provoke a senescence arrest. By contrast, in Rb-deficient fibroblasts, expression of PIASy leads to p53-dependent apoptosis. Induction of senescence requires PIASy E3 activity and is specific for this member of the PIAS ligase family. PIASy stimulates sumoylation and transcriptional activity of p53 and increases Rb-dependent corepression through recruitment to E2F-responsive promoters. Viral oncoprotein E6 suppresses both PIASy-induced senescence and sumoylation of PIASy substrates. Finally, we show that fibroblasts lacking PIASy exhibit a highly reduced propensity to undergo senescence in response to a prosenescence stimulus. Altogether, these data provide the first evidence for a direct role of an E3 SUMO ligase, and by implication of the SUMO pathway, in cellular senescence and apoptosis. 

Retracted: Yes

PubPeer comments:
 Figure 6H. Unexpected symmetry. ![file] , 
 Figure 6F. Much more similar than you would expect. https: imgur.com 4eDiqj5 , 
 #1 Figure 6H. PIASy panel. All the bands look very similar. ![file] , 
 Figure 4B. Much more similar than you would expect. ![file] , 
 Figures 4Dand 4E. More similar than you would expect. https: imgur.com Jvh642N , 
 Figure 2D. Much more similar than you would expect. https: imgur.com 7IuLjFv , 
 Figure 4A. Much more similar than you would expect. https: imgur.com DxsF0ju , 
 Figure 4A. Much more similar than you would expect. ![file] , 
 We thank PubPeer for bringing this issue to our attention. I am in contact with the co-authors to address this matter and will be back to PubPeer later. Sincerely, Anne Dejean , 
 #5 Additional problematic data figure 4E. Much more similar than you would expect. https: imgur.com JMONpjU , 
 Figure 3. Straight edges in some panels, but not in others. ![file] , 
 2020 retraction notice. https: www.cell.com molecular-cell fulltext S1097-2765(20)30891-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276520308911%3Fshowall%3Dtrue We, the authors, were made aware of irregularities in western blots shown in the article. We have further investigated the matter and found that the paper contains multiple examples of incorrect data use in Figures 2D, 4A, 4B, 4E, 6F, and 6H, including duplications and image flipping. All of these figures were assembled by the first author (O.B.). The authors are thus retracting the paper. We sincerely apologize to the scientific community for any inconvenience resulting from the publication and subsequent retraction of this article. All the authors have agreed to this retraction. ,