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SIAH proteins: Critical roles in leukemogenesis.
MedLine Citation:
PMID:  23038274     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The delicate balance between the synthesis and the degradation of proteins ensures cellular homeostasis. Proteases act in an irreversible manner and therefore have to be strictly regulated. The ubiquitin-proteasome-system (UPS) is a major pathway for the proteolytic degradation of cellular proteins. Since dysregulation of the UPS is observed in most cancers including leukemia, the UPS is a valid target for therapeutic intervention strategies. Ubiquitin-ligases selectively bind substrates to target them for poly-ubiquitinylation and proteasomal degradation. Therefore, pharmacological modulation of these proteins could allow a specific level of control. Increasing evidence accumulates that ubiquitin-ligases termed mammalian seven in absentia homologues (SIAHs) are not only critical for the pathogenesis of solid tumors but also for leukemogenesis. However, the relevance and therapeutic potential of SIAH-dependent processes has not been fully elucidated. Here, we summarize functions of SIAH ubiquitin-ligases in leukemias, how they select leukemia-relevant substrates for proteasomal degradation, and how the expression and activity of SIAH1 and SIAH2 can be modulated in vivo. We also discuss that epigenetic drugs belonging to the group of histone deacetylase inhibitors induce SIAH-dependent proteasomal degradation to accelerate the turnover of leukemogenic proteins. In addition, our review highlights potential areas for future research on SIAH proteins.Leukemia accepted article preview online, 5 October 2012; doi:10.1038/leu.2012.284.
Authors:
O H Krämer; R H Stauber; G Bug; J Hartkamp; S K Knauer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-05
Journal Detail:
Title:  Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K     Volume:  -     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Center for Molecular Biomedicine (CMB), Department of Biochemistry, University of Jena, Jena, Germany.
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