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.
Kim
Se-Yong
SY
Department of Biological Science, Sungkyunkwan University, 300 Chunchundong, Suwon 440-746, Republic of Korea.
Choi
Dong Wook
DW
Kim
Eun-A
EA
Choi
Cheol Yong
CY
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014763:Viral Matrix Proteins / Q000378:metabolism; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; D000098563:Seven in Absentia Proteins
D002352:Carrier Proteins; D020930:MAP Kinase Kinase Kinases; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D014763:Viral Matrix Proteins; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; D000098563:Seven in Absentia Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C115114:HIPK2 protein, human