DERP6 (ELP5) and C3ORF75 (ELP6) Regulate Tumorigenicity and Migration of Melanoma Cells as Subunits of Elongator
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
DERP6 (ELP5) and C3ORF75 (ELP6) Regulate Tumorigenicity and Migration of Melanoma Cells as Subunits of Elongator. / Close, Pierre; Gillard, Magali; Ladang, Aurélie; Jiang, Zheshen; Papuga, Jessica; Hawkes, Nicola; Nguyen, Laurent; Chapelle, Jean Paul; Bouillenne, Fabrice; Svejstrup, Jesper; Fillet, Marianne; Chariot, Alain.
I: Journal of Biological Chemistry, Bind 287, Nr. 39, 2012, s. 32535-32545.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - DERP6 (ELP5) and C3ORF75 (ELP6) Regulate Tumorigenicity and Migration of Melanoma Cells as Subunits of Elongator
AU - Close, Pierre
AU - Gillard, Magali
AU - Ladang, Aurélie
AU - Jiang, Zheshen
AU - Papuga, Jessica
AU - Hawkes, Nicola
AU - Nguyen, Laurent
AU - Chapelle, Jean Paul
AU - Bouillenne, Fabrice
AU - Svejstrup, Jesper
AU - Fillet, Marianne
AU - Chariot, Alain
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M112.402727
DO - 10.1074/jbc.M112.402727
M3 - Journal article
C2 - 22854966
AN - SCOPUS:84866544574
VL - 287
SP - 32535
EP - 32545
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 39
ER -
ID: 330899152