Disease relevance of RND3

• CONCLUSION: In conclusion, our findings suggest RhoE as a tumor suppressor gene that is downregulated early in the development of prostate cancer [1].

High impact information on RND3

• Recent evidence has shown that Rnd3 (RhoE) is also involved in the regulation of cell-cycle progression and transformation, indicating that these proteins might have other, as yet unexplored roles [2].
• Expression of Rnd1 or Rnd3/RhoE in fibroblasts inhibits the formation of actin stress fibers, membrane ruffles, and integrin-based focal adhesions and induces loss of cell-substrate adhesion leading to cell rounding (hence Rnd for "round") [3].
• RhoE expression induced a loss of stress fibers and cell rounding, but these effects were only transient [4].
• We have generated fibroblasts with inducible RhoE expression to investigate the role of RhoE in cell proliferation [4].
• RhoE induction inhibited cell proliferation and serum-induced S-phase entry [4].

Biological context of RND3

• A significant increase of RND2 and RND3 protein expression was observed in pregnant relative to nonpregnant myometrium associated with a loss of PPP1R12A phosphorylation [5].
• Thus, RhoE is anticipated to function by regulating ROCK I signaling to control the balance between cell survival and cell death in response to genotoxic stress [6].
• As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins [7].
• We investigated the expression of RhoE and its role in cell cycle regulation and apoptosis in the human prostate [1].
• In addition, apoptotic cell death as measured by a cleavage product of caspase 3 is significantly increased in RhoE-overexpressing cells [1].

Anatomical context of RND3

• When transfected into COS-7 cells, Socius is translocated to the cell periphery in response to Rnd1 and Rnd3 and colocalized with the GTPases [8].
• Silencing of RhoE induction in response to genotoxic stress maintains stress fiber formation and strikingly increases apoptosis, implying an antagonistic role for RhoE in p53-dependent apoptosis [6].
• Indeed, we have found that RhoE in farnesylated in vivo and that this modification is required for association with the plasma membrane and with an unidentified cellular structure that may play a role in adhesion [7].
• Rnd3/RhoE induces tight junction formation in mammary epithelial tumor cells [9].
• RESULTS: Immunoblot analysis showed a strong RhoE signal in both, benign epithelial and stromal cells [1].

Associations of RND3 with chemical compounds

• RhoE Is a Pro-Survival p53 Target Gene that Inhibits ROCK I-Mediated Apoptosis in Response to Genotoxic Stress [6].
• Treatment with the ROCK inhibitor Y-27632 ablated both the glucocorticoid-induced and Rnd3-mediated stimulation in tight junction sealing [10].
• In Con8 cells, the glucocorticoid induced formation of tight junctions requires the steroid-mediated down-regulation RhoA and function of the RhoA antagonist Rnd3 [10].
• Consistent with its inhibitory effect on cell cycle progression, RhoE expression was induced by cisplatin, a DNA damage-inducing agent [4].
• Moreover, IL-8 and RhoE were found to be down-regulated by estradiol at the protein level as well [11].

Other interactions of RND3

• Here we identified Rnd3/RhoE, a GTPase-deficient Rho family member and RhoA antagonist, as a key regulator of apical junction dynamics [9].
• RhoE also acts independently of ROCK to inhibit cell cycle progression, in part by preventing translation of cyclin D1, and to inhibit transformation of fibroblasts by oncogenic H-Ras [12].

Analytical, diagnostic and therapeutic context of RND3

• On RT-PCR and microarray analysis, RhoE mRNA expression was significantly reduced in malignant tissue when compared to benign samples [1].
• METHODS: RhoE expression in cell lines and tissue specimens was assessed by immunoblot analysis, real-time PCR (RT-PCR), and immunohistochemistry [1].
• The role of RhoE in regulating actin organization was investigated by microinjection in Bac1.2F5 macrophages and MDCK cells [13].

References