News Team Expression Génétique et Développement

(2022, June) Master internship - Spring, 2023. Characterization of two PFDN5 isoforms in Head and Neck Squamous Cell Carcinoma

Contact: Xavier Le Goff (xavier [dot] le-goffatuniv-rennes1 [dot] fr) and Franck Chesnel (franck [dot] chesnelatuniv-rennes1 [dot] fr)

Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer in France with over 14,000 new cases each year. The PFDN5 protein is involved in these cancers, both as a subunit of a prefoldin chaperone complex (PFD) and independently of this complex. However, understanding the link between PFDN5 and tumorigenesis or tumor aggressiveness is complicated by the existence of two isoforms of this protein that are produced by alternative splicing. The expression of these two isoforms correlates with different prognoses of HNSCC patients. During this internship, we propose to characterize the differential functions of the two protein isoforms by determining their interactome. Molecular chaperones are a highly conserved family of proteins that play a central role in the maintenance of protein homeostasis. Many chaperones, including subunits of the PFD complex, are overexpressed in different types of cancer. However, the substrates of PFD, and the resulting cellular functions, remain largely unknown. We will use a combination of proximity biotinylation (BioID) and affinity purification followed by mass spectrometry (AP-MS) to characterize the interactome of each PFDN5 isoform in HNSCC cell lines. The resulting network will allow to better identify the specific functions of each PFDN5 isoform, both within and independent of the PFD complex. This work will allow the development of functional hypotheses on the contribution of PFDN5 in tumorigenesis.

(2020, October) Yannick Arlot partner of an ANR grant

This 3-year project is carried by Betty Gardie, Nantes

(2020, October) Publication in PLoS Genetics: the degradation of the tumor suppressor VHL

(2020, June): A new publication with our partner Salil Lachke

This fruitful collaboration has already resulted in 3 joint publications. Matthieu Duot will start a PhD co-directed by the two teams in October 2020. The work together continues!