Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

New insights into the function and regulation of the PAQosome chaperone complex (#481)

Philippe Cloutier 1 , Christian Poitras 1 , Marie-Soleil Gauthier 1 , Benoit Coulombe 1
  1. Institut de recherches cliniques de Montréal (IRCM), Montreal, QUEBEC, Canada

Since its discovery a little over a decade ago, the PAQosome (also known as R2TP/PFDL) has emerged as a critical organizer in the biogenesis of several protein complexes and networks such as protein assemblies involved in transcription, mRNA maturation, translation and nutrient-sensitive signalling pathways. Unsurprisingly, evidence is mounting that this chaperone complex may be involved in tumorigenesis, consistent with a role in regulating proliferation. We present here our most recent results that led to the identification of new client protein complexes and novel post-translational modification (PTM)-based modes of regulation of the PAQosome. Similar to what has recently been reported for axonemal dynein complexes involved in cilium motility; we now identify cytoplasmic dynein complexes that are responsible for cargo transport along microtubules as new clients of the PAQosome. We have also identified a phosphorylation-dependent association of the PAQosome subunit RPAP3 with preribosome complexes. Additionally, we report for the first time the identification of a small ORF-encoded PAQosome subunit, along with a possible role in the regulation of downstream gene, asparagine synthetase (ASNS) whose expression is linked to neurological disorders and response to asparaginase, a chemotherapeutic drug used in the treatment of acute lymphoblastic leukemia (ALL). These results define novel aspects of PAQosome function and regulation, some being associated with human diseases.