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Impaired PIASy-Tip60 signaling weakens activation of p53 in melanoma.
MedLine Citation:
PMID:  23624367     Owner:  NLM     Status:  In-Data-Review    
The tumor suppressor p53 plays a central role in preventing tumor development by promoting transcription of genes that stall cell cycle and induce cell death. Although the majority of melanomas express wild-type p53, the molecular mechanisms that impede its activation remain unclear. We previously reported that the SUMO E3 ligase PIASy and the histone acetyltransferase Tip60 signaling cascade promote p53-dependent autophagy and apoptosis. We hypothesized that impairment in this signaling attenuates p53, thus disabling its apoptotic function in melanoma. Here, we show that human melanoma patient samples and cell lines maintain p53 expression but PIASy and/or Tip60 are frequently lost. We observed dysregulation of Tip60-mediated p53 transcription program in melanoma cell lines. Reconstitution of PIASy and Tip60 in melanoma cells increased genotoxic stress-induced apoptosis. Our study provides a clinical link of how sumoylation signaling may activate p53-mediated cell death in melanoma.
Alexander J Lakhter; Sriramana Kanginakudru; Simon Warren; Christopher E Touloukian; Raymond E Boissy; Samisubbu R Naidu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Melanoma research     Volume:  23     ISSN:  1473-5636     ISO Abbreviation:  Melanoma Res.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  213-7     Citation Subset:  IM    
Departments of aDermatology bSurgery, Indiana University School of Medicine, Indianapolis, Indiana cDepartment of Dermatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
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