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A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent activation

Oncogene volume 26, pages 6665–6676 (2007)Cite this article

Abstract

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.

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Abbreviations

aa:

amino acid

Ab:

antibody

CHX:

cycloheximide

E3:

E3-ubiquitin-protein ligase

hSiah:

human homologues of seven in absentia

Pias:

proteins inhibitor of activated STAT

SUMO:

small ubiquitin-related modifiers

Ub:

ubiquitin

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Acknowledgements

AD is the recipient of a fellowship from the Association pour la Recherche Contre le Cancer (ARC). This work is supported by grants from the ARC and La Ligue Nationale contre le Cancer (France). We acknowledge technical support provided in sequencing by F Letourneur's group (Cochin Institute).

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  1. A Germani

    Present address: 3Current address: Laboratorio di patologia vascolare, IDI, Via Monti di Creta 104, 00167 Roma, Italy.,

Authors and Affiliations

  1. Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France

    A Depaux, F Regnier-Ricard, A Germani & N Varin-Blank

  2. Inserm, U567, Paris, France

    A Depaux, F Regnier-Ricard, A Germani & N Varin-Blank

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  1. A Depaux
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Correspondence to N Varin-Blank.

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Depaux, A., Regnier-Ricard, F., Germani, A. et al. A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent activation. Oncogene 26, 6665–6676 (2007). https://doi.org/10.1038/sj.onc.1210486

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