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Joshi, S; Wels, C; Beham-Schmid, C; Fukunaga-Kalabis, M; Holmen, SL; Otte, M; Herlyn, M; Waldhoer, M; Schaider, H.
Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma.
Int J Cancer. 2015; 137(6):1503-1508 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Beham-Schmid Christine
Joshi Shripad Prakash
Schaider Helmut
Waldhoer Maria
Wels Christian
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Number of Figures: 2
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Abstract:
US28, a constitutively active G-protein-coupled receptor encoded by the human cytomegalovirus, leads to mechanistically unknown programmed cell death. Here we show that expression of wild-type US28 in human melanoma cells leads to apoptotic cell death via caspase 3 activation along with reduced cell proliferation. Reduced tumor growth upon US28 expression was observed in a xenograft mouse model. The signaling mute US28R129A showed a reduced antiproliferative effect. On evaluating different G-proteins coupled to US28 for signal transduction, Gα13 was identified as the main G-protein executing the apoptotic effect. Silencing of Gα13 but not Gαq resulted in a substantial increase in cell survival. Overexpression of Gα13 but not Gαq and their GTPase deficient forms Gα13Q226L and GαqQ209L, respectively, confirmed the requirement of Gα13 for US28 mediated cell death. Increasing expression of Gα13 alone induced cell death underscoring its relay function for US28 mediated decreased cell viability. Further reduced expression of Gα13 in melanoma cell lines isolated from advanced lesions and melanoma tissue was observed. These findings identified Gα13 as crucial for US28-induced cell death, substantiating that the effect of US28 on cell fate depends on preferred G-protein binding. © 2015 UICC.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Apoptosis - physiology
COS Cells -
Caspase 3 - metabolism
Cell Death - physiology
Cell Line -
Cell Line, Tumor -
Cell Proliferation - physiology
Cell Survival - physiology
Cercopithecus aethiops -
Cytomegalovirus - metabolism
GTP-Binding Protein alpha Subunits, G12-G13 - metabolism
GTP-Binding Proteins - metabolism
HEK293 Cells -
Humans -
Melanoma - metabolism
Mice -
NIH 3T3 Cells -
Receptors, Chemokine - metabolism
Signal Transduction - genetics
Viral Proteins - metabolism

Find related publications in this database (Keywords)
US28
viral receptor
cell death
GNA13
melanoma
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