Premium
A Novel Role of RGS6 In Oncogenic Ras‐Induced Cellular Transformation
Author(s) -
Huang Jie,
Yang Jianqi,
Hagen Jussara,
Quelle Dawn,
Fisher Rory
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.498.5
RGS (Regulator of G protein Signaling) proteins are defined by a semi‐conserved RGS domain that bestows their GAP activity toward heterotrimeric GƒÑ subunits. Despite their presumed role as negative regulators of G protein signaling, the precise physiological function of all but a few RGS proteins remains unknown. Based upon a link between a reduction in cancer risk for humans expressing an RGS6 SNP leading to its increased translation, we hypothesized that RGS6 may protect against carcinogenesis. We investigated the role of RGS6 in DNA damage signaling induced by doxorubicin (DXR), one of the most widely used and most effective chemotherapeutic agents, and found that RGS6 is induced by DXR and is required for the ability of DXR to activate/up‐regulate tumor suppressor p53. Here we show that RGS6 is also induced by oncogenic Ras. Mouse embryonic fibroblasts (MEFs) isolated from RGS6 null mice exhibited a faster growth rate and formed more colonies in soft agar colony assays compared to those from WT mice after combined oncogenic Ras activation and p53 inhibition. Thus, RGS6 is induced by oncogenic stimuli and functions to block oncogenic transformation of cells. These findings provide the first evidence for a tumor suppressor role of a member of the RGS protein family. (NIH GM075033, GM075033‐03S1)