HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The human Rgr oncogene is overexpressed in T-cell malignancies and induces transformation by acting as a GEF for Ras and Ral.

Abstract
The Ras superfamily of GTPases is involved in the modification of many cellular processes including cellular motility, proliferation and differentiation. Our laboratory has previously identified the RalGDS-related (Rgr) oncogene in a DMBA (7,12-dimethylbenz[α]anthracene)-induced rabbit squamous cell carcinoma and its human orthologue, hRgr. In this study, we analyzed the expression levels of the human hRgr transcript in a panel of human hematopoietic malignancies and found that a truncated form (diseased-truncated (Dtr-hrgr)) was significantly overexpressed in many T-cell-derived neoplasms. Although the Rgr proto-oncogene belongs to the RalGDS family of guanine nucleotide exchange factors (GEFs), we show that upon the introduction of hRgr into fibroblast cell lines, it is able to elicit the activation of both Ral and Ras GTPases. Moreover, in vitro guanine nucleotide exchange assays confirm that hRgr promotes Ral and Ras activation through GDP dissociation, which is a critical characteristic of GEF proteins. hRgr has guanine nucleotide exchange activity for both small GTPases and this activity was reduced when a point mutation within the catalytic domain (CDC25) of the protein, (cd) Dtr-hRgr, was utilized. These observations prompted the analysis of the biological effects of hRgr and (cd) hRgr expression in cultured cells. Here, we show that hRgr increases proliferation in low serum, increases invasion, reduces anchorage dependence and promotes the progression into the S phase of the cell cycle; properties that are abolished or severely reduced in the presence of the catalytic dead mutant. We conclude that the ability of hRgr to activate both Ral and Ras is responsible for its transformation-inducing phenotype and it could be an important contributor in the development of some T-cell malignancies.
AuthorsK Osei-Sarfo, L Martello, S Ibrahim, A Pellicer
JournalOncogene (Oncogene) Vol. 30 Issue 34 Pg. 3661-71 (Aug 25 2011) ISSN: 1476-5594 [Electronic] England
PMID21441953 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RNA, Messenger
  • ral Guanine Nucleotide Exchange Factor
Topics
  • Cell Transformation, Neoplastic
  • Humans
  • Immunophenotyping
  • Leukemia, T-Cell (genetics)
  • Oncogenes
  • Proto-Oncogene Mas
  • RNA, Messenger (genetics)
  • ral Guanine Nucleotide Exchange Factor (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: