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J Biol Chem. 2012 Sep 21;287(39):32535-45.
DERP6 (ELP5) and C3ORF75 (ELP6) regulate
tumorigenicity and migration of melanoma cells as
subunits of Elongator.
Close P, Gillard M, Ladang A, Jiang Z, Papuga J, Hawkes N, Nguyen L, Chapelle JP, Bouillenne F,
Svejstrup J, Fillet M, Chariot A.
Abstract
The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII trans-
cript elongation through histone acetylation in the nucleus as well as tRNA modifcation in
the cytoplasm. This acetyltransferase complex directly or indirectly regulates numerous bio-
logical processes ranging from exocytosis and resistance to heat shock in yeast to cell migra-
tion and neuronal diferentiation 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 signifcantly decreased upon Elongator deple-
tion 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.
Elongator is a six-subunits complex harbouring an acetyltransferase activity through ELP3. In yeast, the
Elp4,5,6 subcomplex shows an heterohexameric ring-like structure, as illustrated. In this study, we puri-
fed the human Elongator complex (right panel) and characteriezd DERP6 and C3ORF75 as human ELP5
and ELP6, respectively. We further highlighted the crucial role of Elongator subunits in tumorigenicity as
well as in the invasion of melanoma-derived cells.