title: DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator.
abstract: The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This acetyltransferase complex directly or indirectly regulates numerous biological processes ranging from exocytosis and resistance to heat shock in yeast to cell migration and neuronal differentiation in higher eukaryotes. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. Here, we report that DERP6 (ELP5) and C3ORF75 (ELP6) encode these subunits of human Elongator. We further investigated the importance and function of these two subunits by a combination of biochemical analysis and cellular assays. Our results show that DERP6/ELP5 is required for the integrity of Elongator and directly connects ELP3 to ELP4. Importantly, the migration and tumorigenicity of melanoma-derived cells are significantly decreased upon Elongator depletion through ELP1 or ELP3. Strikingly, DERP6/ELP5 and C3ORF75/ELP6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/ELP5 and C3ORF75/ELP6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator.
authors.affiliation: Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, CHU, Sart-Tilman, B-4000 Liège, Belgium. Pierre.Close@ulg.ac.be
authors.forename: Pierre
authors.initials: P
authors.lastname: Close
authors.forename: Magali
authors.initials: M
authors.lastname: Gillard
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ladang
authors.forename: Zheshen
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jessica
authors.initials: J
authors.lastname: Papuga
authors.forename: Nicola
authors.initials: N
authors.lastname: Hawkes
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chapelle
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bouillenne
authors.forename: Jesper
authors.initials: J
authors.lastname: Svejstrup
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
authors.forename: Alain
authors.initials: A
authors.lastname: Chariot
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D017353:Gene Deletion; D057809:HEK293 Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C515617:ELP5 protein, human; C576637:ELP6 protein, human; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D011506:Proteins; D051548:Histone Acetyltransferases; D012319:RNA Polymerase II