Abstract
Homeodomain-interacting protein kinase 2 (HIPK2) induces apoptosis and, thus, is maintained at a low level via ubiquitin-mediated proteolysis. In a yeast two-hybrid screen, we identified Siah1, a RING finger E3 ubiquitin ligase, as an interacting protein of HIPK2. Siah1 targeted HIPK2 for poly-ubiquitination-mediated proteasomal degradation. Degradation of HIPK2 by Siah1 was blocked by forced expression of either Mixed Lineage Kinase-3 or Epstein-Barr viral protein LMP-1, as well as by DNA damaging stimuli. These findings effectively illustrate the regulatory mechanisms underlying HIPK2 stabilization by escape from Siah1-mediated degradation, and that Siah1 is an integration target for several internal or external stimuli for HIPK2 stabilization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Chlorocebus aethiops
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Humans
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MAP Kinase Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinase Kinase Kinase 11
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Mutation
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Stability
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Signal Transduction
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Two-Hybrid System Techniques
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination
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Viral Matrix Proteins / metabolism
Substances
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Carrier Proteins
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EBV-associated membrane antigen, Epstein-Barr virus
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Nuclear Proteins
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Viral Matrix Proteins
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Ubiquitin-Protein Ligases
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seven in absentia proteins
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HIPK2 protein, human
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase Kinases
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Proteasome Endopeptidase Complex