Stabilization of HIPK2 by escape from proteasomal degradation mediated by the E3 ubiquitin ligase Siah1.

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.
Mesh Terms:
Animals, Carrier Proteins, Cell Line, Cercopithecus aethiops, Humans, MAP Kinase Kinase Kinases, Mutation, Nuclear Proteins, Proteasome Endopeptidase Complex, Protein Binding, Protein Stability, Protein-Serine-Threonine Kinases, Signal Transduction, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases, Ubiquitination, Viral Matrix Proteins
Cancer Lett.
Date: Jul. 08, 2009
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