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In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin.
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MedLine Citation:
PMID:  8760875     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alpha-Amanitin is a well-known specific inhibitor of RNA polymerase II (RNAPII) in vitro and in vivo. It is a cyclic octapeptide which binds with high affinity to the largest subunit of RNAPII, RPB1. We have found that in murine fibroblasts exposure to alpha-amanitin triggered degradation of the RPB1 subunit, while other RNAPII subunits, RPB5 and RPB8, remained almost unaffected. Transcriptional inhibition in alpha-amanitin-treated cells was slow and closely followed the disappearance of RPB1. The degradation rate of RPB1 was alpha-amanitin dose dependent and was not a consequence of transcriptional arrest. Alpha-Amanitin-promoted degradation of RPB1 was prevented in cells exposed to actinomycin D, another transcriptional inhibitor. Epitope-tagged recombinant human RPB1 subunits were expressed in mouse fibroblasts. In cells exposed to alpha-amanitin the wild-type recombinant subunit was degraded like the endogenous protein, but a mutated alpha-amanitin-resistant subunit remained unaffected. Hence, alpha-amanitin did not activate a proteolytic system, but instead its binding to mRPB1 likely represented a signal for degradation. Thus, in contrast to other inhibitors, such as actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, which reversibly act on transcription, inhibition by alpha-amanitin cannot be but an irreversible process because of the destruction of RNAPII.
Authors:
V T Nguyen; F Giannoni; M F Dubois; S J Seo; M Vigneron; C Kédinger; O Bensaude
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nucleic acids research     Volume:  24     ISSN:  0305-1048     ISO Abbreviation:  Nucleic Acids Res.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-10-10     Completed Date:  1996-10-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0411011     Medline TA:  Nucleic Acids Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2924-9     Citation Subset:  IM    
Affiliation:
Laboratoire de Génétique Moléculaire, Ecole Normale Superieure, Paris.
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MeSH Terms
Descriptor/Qualifier:
Amanitins / pharmacology*
Amino Acid Sequence
Animals
Cell Nucleus / metabolism
Cells, Cultured
Dactinomycin / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology*
Fibroblasts / cytology
Humans
Intercalating Agents / pharmacology
Mice
Molecular Sequence Data
Protein Conformation
RNA Polymerase II / antagonists & inhibitors*,  genetics,  metabolism*
Recombinant Proteins / metabolism
Transcription, Genetic / drug effects
Chemical
Reg. No./Substance:
0/Amanitins; 0/Enzyme Inhibitors; 0/Intercalating Agents; 0/Recombinant Proteins; 50-76-0/Dactinomycin; EC 2.7.7.-/RNA Polymerase II
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Nucleic Acids Res
ISSN: 0305-1048
ISSN: 1362-4962
Article Information
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Print publication date: Day: 1 Month: 8 Year: 1996
Volume: 24 Issue: 15
First Page: 2924 Last Page: 2929
ID: 146057
PubMed Id: 8760875
Publisher Item Identifier: 6w0070

In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin.
V T Nguyen
F Giannoni
M F Dubois
S J Seo
M Vigneron
C K?dinger
O Bensaude
Laboratoire de G?n?tique Mol?culaire, Ecole Normale Superieure, Paris.


Article Categories:
  • Research Article


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