DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator

[en] 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 melanomaderived 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.

Research center :

Giga-Signal Transduction - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Close, Pierre ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Gillard, Magali

Ladang, Aurélie ; Université de Liège - ULiège > GIGA - Membres

Jiang, Zheshen ; Université de Liège - ULiège > GIGA - Membres

Papuga, Jessica ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Hawkes, Nicola

Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie

CHAPELLE, Jean-Paul ; Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale

Bouillenne, Fabrice ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Svejstrup, Jesper

Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Language :

English

Title :

DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator

Publication date :

01 August 2012

Journal title :

Journal of Biological Chemistry

ISSN :

0021-9258

eISSN :

1083-351X

Publisher :

American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.jbc.org/content/early/2012/08/01/jbc.M112.402727

Available on ORBi :

since 03 August 2012

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