Ras gene mutation has been observed in more than 30%of cancers,and 90%of pancreatic,lung and colon cancers.Ras proteins(K-Ras,H-Ras,N-Ras)act as molecular switches which are activated by binding to GTP.They play a rol...Ras gene mutation has been observed in more than 30%of cancers,and 90%of pancreatic,lung and colon cancers.Ras proteins(K-Ras,H-Ras,N-Ras)act as molecular switches which are activated by binding to GTP.They play a role in the cascade of cell process control(proliferation and cell division).In the inactive state,transforming GTP to GDP leads to the activation of GTpase in Ras gene.However,the mutation in Ras leads to the loss of internal GTPase activity and permanent activation of the protein.The activated Ras can promote the cell death or stop cell growth,which are facilitated by Ras-association domain family.Various studies have been conducted to determine the importance of losing RASSF proteins in Rasinduced tumors.This paper examines the role of Ras and RASSF proteins.In general,RASSF proteins can be used as a suitable means for targeting a large group of Ras-induced tumors.展开更多
Actinorhizal plants contain numerous antioxidants that may play a crucial role in preventing the formation of tumors.H-Ras p21,a member of the Ras-GTPase family,is a promising target to treat various kinds of cancers....Actinorhizal plants contain numerous antioxidants that may play a crucial role in preventing the formation of tumors.H-Ras p21,a member of the Ras-GTPase family,is a promising target to treat various kinds of cancers.An in silico docking study was carried out to identify the inhibitory potential of compounds of these plants against H-Ras by using Discovery Studio 3.5 and by using Autodock 4.2.Docking studies revealed that four compounds,isorhamnetin-7-rhamnoside,quercetin-3-glucoside-7-rhamnoside（present in H.rhamnoides）,zeaxanthin,and translutein（present in H.salicifolia） significantly bind with binding energies-17.1534,-14.7936,-10.2105 and-17.2217 Kcal/mol,respectively,even though they slightly deviate from Lipinski＇s rule.Absorption,distribution,metabolism,excretion and toxicity（ADME/tox） analyses of these compounds and their stereoisomers showed that they were less toxic and non-mutagenic.Amongst them,isorhamntein-7-rhamnoside showed hepatotoxicity.Hence,these compounds can be further investigated in vivo to optimize their formulation and concentration and to develop potential chemical entities for the prevention and treatment of cancers.展开更多
H-Ras is well known as one of the essential components of Ras/Raf/MEK/ERK cascade, which is a critical prosurvival signaling mechanism in most eukaryotic cells. Ras targets Raf/MEK/ERK cascade by integrating and trans...H-Ras is well known as one of the essential components of Ras/Raf/MEK/ERK cascade, which is a critical prosurvival signaling mechanism in most eukaryotic cells. Ras targets Raf/MEK/ERK cascade by integrating and transmitting extracellular signals from growth factor receptors to Raf, leading to the propagation of signals to modulate a serious of cellular survival events. Apoptosis signal-regulating kinasel (ASK1) serves as a general mediator of cell death because it is responsive to a variety of death signals. In this study, we found that H-Ras interacted with ASK1 to cause the inhibition of both ASK1 activity and ASK1-induced apoptosis in vivo, which was reversed only partially by addition of RafS621A, an antagonist of Raf, whereas MEK inhibitor, PD98059, and PI3K inhibitor, LY294002, did not disturb the inhibitory effect of H-Ras on ASK-1-induced apoptosis. Furthermore, by means of immunoprecipitate and kinase assays, we demonstrated that the interaction between H-Ras and ASK1 as well as the inhibition of ASK1 activity were dependent on the binding activity of H-Ras. These results suggest that a novel mechanism may be involved in H-Rasmediated cell survival in addition to the well established MEK/ERK and PI3K/Akt kinase-dependent enhancement of cell survival.展开更多
文摘Ras gene mutation has been observed in more than 30%of cancers,and 90%of pancreatic,lung and colon cancers.Ras proteins(K-Ras,H-Ras,N-Ras)act as molecular switches which are activated by binding to GTP.They play a role in the cascade of cell process control(proliferation and cell division).In the inactive state,transforming GTP to GDP leads to the activation of GTpase in Ras gene.However,the mutation in Ras leads to the loss of internal GTPase activity and permanent activation of the protein.The activated Ras can promote the cell death or stop cell growth,which are facilitated by Ras-association domain family.Various studies have been conducted to determine the importance of losing RASSF proteins in Rasinduced tumors.This paper examines the role of Ras and RASSF proteins.In general,RASSF proteins can be used as a suitable means for targeting a large group of Ras-induced tumors.
文摘Actinorhizal plants contain numerous antioxidants that may play a crucial role in preventing the formation of tumors.H-Ras p21,a member of the Ras-GTPase family,is a promising target to treat various kinds of cancers.An in silico docking study was carried out to identify the inhibitory potential of compounds of these plants against H-Ras by using Discovery Studio 3.5 and by using Autodock 4.2.Docking studies revealed that four compounds,isorhamnetin-7-rhamnoside,quercetin-3-glucoside-7-rhamnoside（present in H.rhamnoides）,zeaxanthin,and translutein（present in H.salicifolia） significantly bind with binding energies-17.1534,-14.7936,-10.2105 and-17.2217 Kcal/mol,respectively,even though they slightly deviate from Lipinski＇s rule.Absorption,distribution,metabolism,excretion and toxicity（ADME/tox） analyses of these compounds and their stereoisomers showed that they were less toxic and non-mutagenic.Amongst them,isorhamntein-7-rhamnoside showed hepatotoxicity.Hence,these compounds can be further investigated in vivo to optimize their formulation and concentration and to develop potential chemical entities for the prevention and treatment of cancers.
文摘H-Ras is well known as one of the essential components of Ras/Raf/MEK/ERK cascade, which is a critical prosurvival signaling mechanism in most eukaryotic cells. Ras targets Raf/MEK/ERK cascade by integrating and transmitting extracellular signals from growth factor receptors to Raf, leading to the propagation of signals to modulate a serious of cellular survival events. Apoptosis signal-regulating kinasel (ASK1) serves as a general mediator of cell death because it is responsive to a variety of death signals. In this study, we found that H-Ras interacted with ASK1 to cause the inhibition of both ASK1 activity and ASK1-induced apoptosis in vivo, which was reversed only partially by addition of RafS621A, an antagonist of Raf, whereas MEK inhibitor, PD98059, and PI3K inhibitor, LY294002, did not disturb the inhibitory effect of H-Ras on ASK-1-induced apoptosis. Furthermore, by means of immunoprecipitate and kinase assays, we demonstrated that the interaction between H-Ras and ASK1 as well as the inhibition of ASK1 activity were dependent on the binding activity of H-Ras. These results suggest that a novel mechanism may be involved in H-Rasmediated cell survival in addition to the well established MEK/ERK and PI3K/Akt kinase-dependent enhancement of cell survival.
