Document Detail


DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator.
MedLine Citation:
PMID:  22854966     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Pierre Close; Magali Gillard; Aurélie Ladang; Zheshen Jiang; Jessica Papuga; Nicola Hawkes; Laurent Nguyen; Jean-Paul Chapelle; Fabrice Bouillenne; Jesper Svejstrup; Marianne Fillet; Alain Chariot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-01
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-24     Completed Date:  2012-12-07     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32535-45     Citation Subset:  IM    
Affiliation:
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, CHU, Sart-Tilman, B-4000 Liège, Belgium. Pierre.Close@ulg.ac.be
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MeSH Terms
Descriptor/Qualifier:
Carrier Proteins / genetics,  metabolism*
Cell Line, Tumor
Cell Movement*
Gene Deletion
HEK293 Cells
Humans
Melanoma / genetics,  metabolism*,  pathology
Multiprotein Complexes / genetics,  metabolism*
Neoplasm Invasiveness
Neoplasm Proteins / genetics,  metabolism*
Proteins / genetics,  metabolism*
RNA Polymerase II / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
//Cancer Research UK
Chemical
Reg. No./Substance:
0/C17orf81 protein, human; 0/Carrier Proteins; 0/ELP6 protein, human; 0/Multiprotein Complexes; 0/Neoplasm Proteins; 0/Proteins; EC 2.7.7.-/RNA Polymerase II
Comments/Corrections

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