A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent activation.
Protein inhibitor of activated STAT (Pias) and human homologues of seven in absentia (hSiah) proteins both exhibit properties of ubiquitin-family peptides conjugating enzymes. Pias present E3-ligase activity for small ubiquitin-related modifiers (Sumo) covalent attachment to their targets. This post-translational modification is responsible for the activation of different transcription factors such as AP1. HSiah proteins possess ubiquitin-E3-ligase activity that triggers their partners to proteasomal-dependent degradation. The present study identifies Pias as a new hSiah2-interacting protein. We demonstrate that hSiah2 regulates specifically the proteasome-dependent degradation of Pias proteins. On reverse, Pias does not prevent hSiah2 degradation. We provide evidences for hSiah2-dependent degradation of Pias as being a mechanism in the regulation of c-jun N-terminal kinase-activating pathways. This report describes a new interconnection between sumoylation and ubiquitination pathways by regulating the levels of the E3-ligases available for these processes.
Depaux
A
A
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Regnier-Ricard
F
F
Germani
A
A
Varin-Blank
N
N
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D000098563:Seven in Absentia Proteins
D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D016755:Proto-Oncogene Proteins c-jun; D025842:SUMO-1 Protein; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D048670:MAP Kinase Kinase 4; D046988:Proteasome Endopeptidase Complex