|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0013138,
umls-concept:C0024660,
umls-concept:C0033684,
umls-concept:C0146495,
umls-concept:C0208355,
umls-concept:C0243125,
umls-concept:C0678594,
umls-concept:C0699900,
umls-concept:C1334043,
umls-concept:C1515175,
umls-concept:C1516692,
umls-concept:C1521761
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2004-2-9
|
|
pubmed:abstractText |
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.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PML protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/seven in absentia proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
13
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
5374-9
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:14645235-Amino Acid Motifs,
pubmed-meshheading:14645235-Amino Acid Sequence,
pubmed-meshheading:14645235-Animals,
pubmed-meshheading:14645235-Blotting, Western,
pubmed-meshheading:14645235-Cell Differentiation,
pubmed-meshheading:14645235-Cell Line,
pubmed-meshheading:14645235-Cysteine Endopeptidases,
pubmed-meshheading:14645235-DNA, Complementary,
pubmed-meshheading:14645235-Drosophila,
pubmed-meshheading:14645235-Genetic Vectors,
pubmed-meshheading:14645235-Humans,
pubmed-meshheading:14645235-Microscopy, Fluorescence,
pubmed-meshheading:14645235-Molecular Sequence Data,
pubmed-meshheading:14645235-Multienzyme Complexes,
pubmed-meshheading:14645235-Mutation,
pubmed-meshheading:14645235-Neoplasm Proteins,
pubmed-meshheading:14645235-Nuclear Proteins,
pubmed-meshheading:14645235-Plasmids,
pubmed-meshheading:14645235-Precipitin Tests,
pubmed-meshheading:14645235-Proteasome Endopeptidase Complex,
pubmed-meshheading:14645235-Protein Binding,
pubmed-meshheading:14645235-Protein Processing, Post-Translational,
pubmed-meshheading:14645235-Protein Structure, Tertiary,
pubmed-meshheading:14645235-Recombinant Fusion Proteins,
pubmed-meshheading:14645235-Transcription, Genetic,
pubmed-meshheading:14645235-Transcription Factors,
pubmed-meshheading:14645235-Transfection,
pubmed-meshheading:14645235-Tumor Suppressor Proteins,
pubmed-meshheading:14645235-U937 Cells,
pubmed-meshheading:14645235-Ubiquitin-Protein Ligases
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome.
|
|
pubmed:affiliation |
Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy. mirco.fanelli@uniurb.it
|
|
pubmed:publicationType |
Journal Article
|
