C3G-mediated suppression of oncogene-induced focus formation in fibroblasts involves inhibition of ERK activation, cyclin A expression and alterations of anchorage-independent growth
In: Oncogene (Basingstoke), Jg. 23 (2004), Heft 28, S. 4885-4893
Online
academicJournal
- print, 48 ref
Zugriff:
We showed previously that exogenous overexpression of C3G, a guanine nucleotide releasing factor (GEF) for Rap1 and R-Ras proteins, blocks the focus-forming activity of cotransfected, activated, sis, ras and v-raf oncogenes in NIH 3T3 cells. In this report, we show that C3G also interferes with dbl and R-Ras focus-forming activity and demonstrate that the transformation suppressor ability of C3G maps to its Crk-binding region (SH3-b domain). Using full-length C3G and C3GΔCat mutant, lacking catalytic domain, we showed here that overexpression of cotransfected C3G or C3GACat inhibited oncogenic Hraslys12-mediated phosphorylation of ERK, without altering Ras and Raf-1 kinase activation. We also showed that, overexpressed C3G and C3GACat inhibited the viability of oncogenic Ras-induced colonies in soft agar, indicating that C3G interferes with the anchorage-independent growth of Ras-transformed cells in a Rap1-independent manner. Consistent with both observations, overexpression of exogenous C3G and C3GΔCat also caused downregulation of Ras-induced cyclin A expression. Altogether, our results indicate that C3G interferes with at least two separate aspects of oncogenic transformation - cell cycle progression and loss of contact inhibition - and that these inhibitory effects probably account for its transformation suppressor activity.
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C3G-mediated suppression of oncogene-induced focus formation in fibroblasts involves inhibition of ERK activation, cyclin A expression and alterations of anchorage-independent growth
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Autor/in / Beteiligte Person: | GUERRERO, Carmen ; MARTIN-ENCABO, Susana ; FERNANDEZ-MEDARDE, Alberto ; SANTOS, Eugenio |
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Zeitschrift: | Oncogene (Basingstoke), Jg. 23 (2004), Heft 28, S. 4885-4893 |
Veröffentlichung: | Basingstoke: Nature Publishing, 2004 |
Medientyp: | academicJournal |
Umfang: | print, 48 ref |
ISSN: | 0950-9232 (print) |
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