Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma

Joshi, Shripad, Wels, Christian, Beham-Schmid, Christine, Fukunaga-Kalabis, Mizuho, Holmen, Sheri L, Otte, Marcus, Herlyn, Meenhard, Waldhoer, Maria and Schaiderm Helmut (2015) Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. International Journal of Cancer, 137 6: 1503-1508. doi:10.1002/ijc.29506

Author Joshi, Shripad
Wels, Christian
Beham-Schmid, Christine
Fukunaga-Kalabis, Mizuho
Holmen, Sheri L
Otte, Marcus
Herlyn, Meenhard
Waldhoer, Maria
Schaiderm Helmut
Title Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 1097-0215
Publication date 2015-03-16
Year available 2015
Sub-type Article (original research)
DOI 10.1002/ijc.29506
Volume 137
Issue 6
Start page 1503
End page 1508
Total pages 6
Place of publication Hoboken, United States
Publisher ohn Wiley & Sons, Inc
Collection year 2016
Language eng
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.
Keyword US28
Viral receptor
Cell death
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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