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- W2072153965 abstract "Selective activation of Rho GTPase cascade requires the release of Rho from RhoGDI (GDP‐dissociation inhibitors) complexes. Our previous studies identified RhoGDIα SUMOylation at Lys‐138 and its function in the regulation of cancer cell invasion. In the current study, we demonstrate that RhoGDIα SUMOylation has a crucial role in the suppression of cancer cell anchorage‐independent growth as well as the molecular mechanisms underlying this suppression. We found that ectopic expression of RhoGDIα resulted in marked inhibition of an anchorage‐independent growth with induction of G0/G1 cell cycle arrest, while point mutation of RhoGDIα SUMOylation at residue Lys‐138 (K138R) abrogated this growth suppression and G0/G1 cell cycle arrest in cancer cells. Further studies showed that SUMOylation at Lys‐138 was critical for RhoGDIα down‐regulation of cyclin D1 protein expression and that MEK1/2‐Erk was a specific downstream target of SUMOylated RhoGDIα for its inhibition of C‐Jun/AP‐1 cascade, cyclin d1 transcription, and cell cycle progression. These results strongly demonstrate that SUMOylated RhoGDIα suppressed C‐Jun/AP‐1‐dependent transactivation specifically via targeting MEK1/2‐Erk, subsequently leading to the down‐regulation of cyclin D1 expression and anti‐cancer activity. Our results provide new mechanistic insights into the understanding of essential role of SUMOylation at Lys‐138 in RhoGDIα's biological function." @default.
- W2072153965 created "2016-06-24" @default.
- W2072153965 creator A5007759793 @default.
- W2072153965 creator A5025524154 @default.
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- W2072153965 creator A5071451676 @default.
- W2072153965 creator A5074463821 @default.
- W2072153965 creator A5083753074 @default.
- W2072153965 creator A5088199873 @default.
- W2072153965 date "2013-12-03" @default.
- W2072153965 modified "2023-10-15" @default.
- W2072153965 title "SUMOylation of RhoGDIα is required for its repression of cyclin D1 expression and anchorage-independent growth of cancer cells" @default.
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- W2072153965 doi "https://doi.org/10.1016/j.molonc.2013.11.006" @default.
- W2072153965 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3943698" @default.
- W2072153965 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24342356" @default.
- W2072153965 hasPublicationYear "2013" @default.
- W2072153965 type Work @default.