Eva Bekesi's research while affiliated with Leidos Biomedical Research, Inc. and other places

... This unique pattern of Mg 2+ dependence may result from sequence divergence in the G3 domain of ARHI. In most other Ras proteins, the highly conserved T 58 , A 59 , and G 60 residues in the G3 domain known to be important for interaction with Mg 2+ /GTP (Willumsen et al., 1986) are replaced in ARHI with S 92 , K 93 , and S 94 residues, respectively. These residues are also important for maintaining GTPase activity in Ras proteins. ...

... Feramisco et al. (1985) reported that microinjection of antibodies specific for a mutant K-Ras protein into NRK cells transformed by V-K-ras gene caused a transient reversion of the cells to a normal phenotype. Similarly, Kung et al. (1986) found that microinjection of a neutralizing monoclonal antibody against H-Ras (Y13-259) neutralized the transforming activity of a coinjected bacterially synthesized H-Ras protein and that the neutralization effect was blocked by coinjection of excess H-Ras protein. In addition, microinjection of Y13-259 into transformed NIH3T3 cells (obtained by DNA transfection of NIH3T3 cells with a mutant H-ras gene) reversed their transformed phenotypes. ...

... Rap1GAP belongs to the family of GTPase activating proteins (GAPs), which accelerate hydrolysis of bound GTP to GDP, to block the activity of small G proteins. Specifically, Rap1GAP suppresses the activation of Rap1, a small G protein with 53% amino acid identity to Ras [23,24]. Members of the Rap1GAP family (Rap1GAPs), including Rap1GAP, Rap1GAPII, signal-induced proliferation-associated gene-1 (SPA-1), spine-associated RapGAP (SPAR), E6-targeted protein 1 (E6TP1) and several SPA-1-like proteins (SPA-Ls), are highly expressed in non-proliferating tissues, such as the nervous system and pancreas [25]. ...

... Extensive earlier biochemical studies revealed that oncogenic RAS mutations cause a reduction of the GTP hydrolysis rate, generating an increased population of Ras GTP (6)(7)(8)(9)(10)(11). This likely leads to an overactivation of the downstream signalling pathways and therefore is considered the major cause of the K-Ras oncogenicity. ...

... Statins inhibit the HMG-CoA reductase (HMGCR) to block mevalonate and subsequent cholesterol production. The resulting decrease in intracellular cholesterol levels triggers a cascade leading to increased cholesterol uptake and degradation in the cells[347][348][349][350][351][352][353]. ...

... Over the last decades, several mutational studies were conducted on Ras and Sos proteins to determine the key amino acids. In 1998, Boriack-Sjodin et al. [43] demonstrated that the contacts between Ras and Sos are mainly mediated by the Switch I and Switch II regions of Ras [43,[49][50][51][52][53][54][55][56][57][58] and are essentially hydrophobic, polar, and charge-charge contacts. Hall et al. [61] performed site-directed mutagenesis to deeply investigate these contacts. ...

... and Binding of P'PlMu-or P'PlHu- IFN-y to Cek-Recombinant Mu-IFN-y with a specific activity of 4.4 X lo6 units/mg and recombinant Hu-IFN-y with a specific activity of 1.1 X lo7 units/mg were isolated from Escherichia coli as described previously (Kumar et al., 1988; Fields et al., 1987). Murine and human IFN-y were phosphorylated as reported (Mariano et al., 1987; Rashidbaigi et al., 1985; Kung and Bekesi et al., 1986). To measure binding of IFN-y to cells, trypsinized cells were resuspended in the medium described above and counted. ...

... It is currently unknown how ρ activity is regulated during periods of slow growth or stress, when translation is inefficient and uncontrolled transcription termination may be detrimental. Cellular levels of ρ are kept almost constant 17 through auto-regulation 18 , implying that during stress, termination may be kept in check by regulators that reduce ρ activity. Three cellular anti-termination factors have been reported to inhibit ρ; the RNA chaperone Hfq, the Ser/Thr kinase YihE and the small protein YaeO (a.k.a. ...

... However, regulation of the GTP bound state of RAS by GAPs alone is difficult to reconcile for several reasons. The p120GAP (also called RASA1) protein cannot compete with Ras effectors, including RAF, under physiological-like conditions (Smith & Ikura, 2014), and it is well documented that RAF blocks GAP activity by binding to RAS (Moodie et al., 1995;Scheffler et al., 1994;Smith & Ikura, 2014;Warne et al., 1993;Zhang et al., 1993). Furthermore, the spectrum of cancers that frequently show NF1 and p120GAP inactivation weakly overlap with those with activating RAS mutations (Consortium APG, 2017). ...