Oncogenic forms of Ras proteins are associated with a broad range of human cancers including an estimated 90% of all colon cancers (1). Ras proteins undergo a complex series of posttranslational processing events, which have been defined over the past several years (2, 3). The initial post-translational event is the transfer of the 15-carbon isoprene farnesyl from farnesyl pyrophosphate to a Cys residue (Cys 186 in Ha-Ras) in the conserved carboxyl-terminal "CAAX" motif (where "A" is an aliphatic residue) present in all Ras proteins (4, 5). Studies employing site-directed mutagenesis (6, 7) or inhibitors of hydroxymethylglutaryl-CoA reductase (8), the rate-limiting enzyme in isoprenoid biosynthesis, demonstrated that isoprenylation is required for Ras proteins to become membraneassociated and to induce cellular transformation. The farnesyl protein transferase (FPT) 1 that catalyzes this reaction has been purified (9) and cDNA clones for its ␣ and  subunits isolated (10 -12).A number of other cellular proteins are also isoprenylated on a Cys residue near their COOH terminus (13,14). These include other substrates for FPT, such as the nuclear lamins (15). However, the majority of cellular isoprenylated proteins are modified with geranylgeranyl, a 20-carbon isoprene. Two distinct geranylgeranyl protein transferases (GGPT I and II) have been identified (16,17) and cDNA clones for their ␣ and  subunits isolated (18,19). GGPT I and FPT share a common ␣ subunit (18,20).The primary determinant for recognition of protein substrates by the isoprenyl transferases is the substrate's carboxyl-terminal amino acid sequence. Proteins ending in Cys-X-XSer (or Met) are preferred substrates for FPT, while proteins terminating in Cys-X-X-Leu are preferred substrates for GGPT I (21, 22). Substitution of leucine for serine at the COOH terminus of the Ha-Ras CAAX box (Ser 189 3 Leu) makes this protein a substrate for geranylgeranylation (rather than farnesylation) both in vitro and in cells (23). The different substrate specificities of FPT and GGPT-1 are likely mediated by their distinct  subunits. GGPT II utilizes protein substrates terminating in Cys-Cys or Cys-X-Cys (17,24).A number of inhibitors of FPT have been reported over the past several years (25). The design of CAAX peptidomimetics (26 -29) has resulted in potent and selective FPT inhibitors capable of blocking Ras processing in cells. These compounds have shown considerable promise as antitumor agents based on their ability to inhibit cellular transformation induced by oncogenic Ras proteins (26,27) and the growth of Ras-dependent
Some of the conformational changes required for infectivity and involved in the control of capsid stability and neurovirulence in mice may occur in the vicinity of the fivefold axis of the poliovirus, where there are significant structural differences among the three poliovirus serotypes in the surface exposed loops of VP1 (BC, DE, and HI). A surface depression is located at the fivefold axis of PV2L that is not present in the other two poliovirus serotypes. The observed interaction of RNA with VP4 supports the observation that loss of VP4 ultimately leads to the loss of viral RNA. A model is proposed that suggests dual involvement of the virion fivefold and pseudo-threefold axes in receptor-mediated initiation of infection by picornaviruses.
HEp-2 cells infected with two laboratory strains (mP and MP) and two freshly isolated strains (F and G) of herpes simplex virus were fixed at intervals between 4 and 50 hr postinfection and sectioned, and were then examined with the electron microscope. These studies revealed the following. (i) All four strains caused identical segregation of nucleoli and aggregation of host chromosomes at the nuclear membrane. (ii) The development of MP virus could not be differentiated from that of its parent mP strain. (iii) There were quantitative differences between laboratory (mP) and freshly isolated (F) type 1 strains. Thus, cells infected with F contained numerous nuclear crystals of nucleocapsids and relatively few cytoplasmic structures containing enveloped nucleocapsids. Conversely, cells infected with mP or with MP virus contained numerous cytoplasmic structures with enveloped nucleocapsids and relatively few nuclear crystals of nucleocapsids. (iv) There were qualitative differences between type 2 strain (G) isolated from genital lesions and type 1 strains. Thus, cells infected with the G strain contain numerous filaments in nuclei and unenveloped and partially enveloped nucleocapsids in the cytoplasm. Of particular interest is the finding that cytoplasmic membranes in apposition to nucleocapsids were thickened and bent as if they were enveloping the particle. The significance of the qualitative differences in the development of the four strains is discussed.
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