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Regulation of Transcription by the Ubiquitin/Proteasome System – 0

Submission summary

Regulation of gene expression is a complex phenomenon involving a large number of cellular factors to control RNA polymerase II activity. This multi-protein transcriptionally active complex is remodeled in both its composition and architecture during the different phases of transcription (initiation, elongation and termination). Mounting evidence indicates that the ubiquitin/proteasome system plays an important role in the regulation of transcription via both proteolytic and non-proteolytic mechanisms. We have recently identified a novel transcriptional co-activator, Proteasomal ATPase Associated Factor 1 (PAAF1), that enhances Tat-dependent transcription from the HIV-1 promoter. PAAF1, together with a subcomplex of the proteasome that we have called '19S-like complex', are recruited by Tat to the HIV-1 promoter to stimulate transcription. PAAF1 induces proteasome dissociation allowing Tat to recruit the 19S-like complex which is required for efficient transcriptional elongation. Preliminary data indicate that PAAF1 is also required for the maturation of RNA transcripts. The research project we propose will extend our initial findings with the specific goals of 1) identifiying cellular gene sequences directly regulated by PAAF1, 26S proteasome and the 19S-like complex 2) purify and characterize PAAF1 and 19S-like complexes involved in transcription 3) determine the molecular mechanisms by which PAAF1 regulates pre-mRNA processing and 4) study the role of a putative ubiquitin interacting motif (UIM) we have identified in PAAF1 in the regulation of its transcriptional activity.

Project coordination

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

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Help of the ANR 0 euros
Beginning and duration of the scientific project: - 0 Months

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