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http://purl.uniprot.org/citations/14645235http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14645235http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14645235http://www.w3.org/2000/01/rdf-schema#comment"Mammalian homologues of Drosophila Seven in Absentia (SIAHs) target for proteasome-mediated degradation several factors involved in cell growth and tumorigenesis. Here we show that SIAH-1/2 binds and targets for proteasome-mediated degradation the putative tumor suppressor and tripartite motif (TRIM) family member PML, leading to the loss of its transcriptional co-activating properties and a reduction in the number of endogenous PML nuclear bodies. Association with PML requires the substrate-binding domain (SBD) of SIAH-1/2 through an interacting surface apparently distinct from those predicted by the structural studies, or shown experimentally to mediate binding to SIAH-associated factors. Within PML, the coiled-coil domain is required for Siah- and proteasome-mediated degradation, and deletions of regions critical for the integrity of this region impair the ability of Siah to trigger PML-RAR degradation. Fusion of the coiled-coil domain to heterologous proteins resulted in the capacity of mSiah-2 to target their degradation. All of the TRIM proteins tested were degraded upon mSiah-2 overexpression. Finally, we show that the fusion protein PML-RAR (that retains the coiled-coil domain), which causes acute promyelocytic leukemias, is also a potential substrate of mSiah-2. As a result of mSiah-2 overexpression and subsequent degradation of the fusion protein, the arrest in hematopoietic differentiation because of expression of PML-RAR is partially rescued. These results identify PML and other TRIMs as new factors post-translationally regulated by SIAH and involve the coiled-coil region of PML and of other SIAH substrates as a novel structural determinant for targeted degradation."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m306407200"xsd:string
http://purl.uniprot.org/citations/14645235http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m306407200"xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Matsuzawa S."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Matsuzawa S."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Pelicci P.G."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Pelicci P.G."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"De Luca P."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"De Luca P."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Lazar M.A."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Lazar M.A."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Minucci S."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Minucci S."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Caprodossi S."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Caprodossi S."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Fanelli M."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Fanelli M."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Fantozzi A."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/author"Fantozzi A."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/14645235http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string