Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation.
The different activities of the tumor suppressor p53 are tightly regulated by various negative and positive feedback loops, which allow accurate control of its function. Here we show that the p53-inducible ubiquitin E3 ligase Siah-1L can bind to the p53 phosphorylating kinase HIPK2 and thus allows its ubiquitination and proteasomal elimination. Siah-1L also eliminates the HIPK family member HIPK3, indicating that its activity is not restricted to one member of the HIPK family. The stimulating effect of HIPK2 on p53-triggered transcription is counteracted by Siah-1L, thus showing the occurrence of another negative feedback loop controlling the p53 response.
Calzado
Marco A
MA
Departmento de Biología Celular, Fisiología e Immunología, Facultad de Medicina, Universidad de Córdoba, Avda. Menéndez Pidal, s/n, E-14004 Córdoba, Spain.
de la Vega
Laureano
L
Muñoz
Eduardo
E
Schmitz
M Lienhard
ML
D017209:Apoptosis; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D025821:Polyubiquitin / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000098563:Seven in Absentia Proteins
D002352:Carrier Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D025821:Polyubiquitin; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D017346:Protein Serine-Threonine Kinases