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Query: UNIPROT:P06889 (Mol)
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Replication of the IncI alpha plasmid ColIb-P9 requires the repZ gene, which encodes an essential, unstable initiator protein termed RepZ. Although many functional features of the ColIb-P9 replicon resemble those of structurally unrelated IncFII plasmids R1 and NR1, the role of transcription of repZ towards the replication origin is poorly understood. Using a series of deletion and substitution mutants of the ColIb-P9 replicon, we found that RepZ prefers to act in cis and that a spacer sequence between repZ and the origin is required for replication. This spacer element, referred to as CIS, retained strong transcription terminator activity. Efficient transcription terminators, whether Rho-dependent or -independent, were capable of replacing CIS function for in vivo replication; ColIb-P9 replicated better as transcription terminated more efficiently within CIS. When the CIS element was substituted for by a strong Rho-dependent terminator, such as lambda tR1 or E. coli trp t', in vivo replication of these recombinant replicons became dependent on the Rho factor, in contrast to the authentic ColIb-P9 replicon.
Mol Microbiol 1995 Jul
PMID:A transcription terminator signal necessary for plasmid ColIb-P9 replication. 749 78

We report the cloning of the RNase P RNA genes from the primary aetiological agent of porcine pneumonia, Mycoplasma hyopneumoniae, and the closely related commensal, Mycoplasma flocculare. The monocistronic genes each have promoters with AT-rich -35 regions and Rho-independent-like transcription terminators which are retained in the RNase P RNA. Both of these RNase P RNA variants are shown to be catalytically active in vitro in spite of a low overall GC content (30%). Our results suggest a new example of a stable mini-helix in the conserved core of the mycoplasmal RNase P RNAs. Deletion of the corresponding structural element in Escherichia coli RNase P RNA (M1 RNA) generated an RNase P RNA with an impaired substrate interaction. Displacement of this structural element with the mycoplasmal mini-helix resulted in an enzyme with a phenotype similar to that of wild-type M1 RNA. In addition, this structural element is important for lead ion-induced cleavage at specific sites in M1 RNA.
Mol Microbiol 1994 Mar
PMID:Cloning and characterization of the RNase P RNA genes from two porcine mycoplasmas. 855 60

The Escherichia coli protein NusG is known to modulate Rho-dependent transcription termination in vivo. We have shown that it can also alter the pattern of Rho-dependent RNA endpoints in vitro, at lower NusG concentrations than can be explained by reported interactions between NusG and Rho or RNA polymerase. Three observations in vitro now suggest a model to account for these effects of NusG on Rho-dependent termination. First, the presence of NusG circumvents the interference with Rho function caused by adding DNA oligonucleotides complementary to particular segments of the Rho binding site. Second, when NusG is added to stalled elongation complexes, the off-rate of Rho from nascent RNA is slowed. Third, NusG associates stably with the elongation complex only when Rho is also present and bound to the nascent RNA. Our observations are consistent with a model in which NusG and Rho participate in an interdependent association with the transcribing RNA polymerase and the nascent RNA to facilitate the recognition and use of termination signals. Common structural and functional features shared with complexes that carry out processive antitermination are discussed.
J Mol Biol 1994 Nov 11
PMID:A quaternary transcription termination complex. Reciprocal stabilization by Rho factor and NusG protein. 752 72

Ral proteins constitute a distinct family of Ras-related GTPases. Although similar to Ras in amino acid sequence, Ral proteins are activated by a unique nucleotide exchange factor and inactivated by a distinct GTPase-activating protein. Unlike Ras, they fail to promote transformed foci when activated versions are expressed in cells. To identify downstream targets that might mediate a Ral-specific function, we used a Saccharomyces cerevisiae-based interaction assay to clone a novel cDNA that encodes a Ral-binding protein (RalBP1). RalBP1 binds specifically to the active GTP-bound form of RalA and not to a mutant Ral with a point mutation in its putative effector domain. In addition to a Ral-binding domain, RalBP1 also contains a Rho-GTPase-activating protein domain that interacts preferentially with Rho family member CDC42. Since CDC42 has been implicated in bud site selection in S. cerevisiae and filopodium formation in mammalian cells, Ral may function to modulate the actin cytoskeleton through its interactions with RalBP1.
Mol Cell Biol 1995 Aug
PMID:Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. 762 49

In animals, the small GTP-binding proteins, Rac and Rho, of the ras superfamily participate in the signal transduction pathway that regulates the organization of the actin cytoskeleton. We report here on the characterization of two distinct cDNA clones isolated from a cotton fiber cDNA library that code for homologs of animal Rac proteins. Using gene-specific probes, we have determined that amphidiploid cotton contains two genes that code for each of the two Rac proteins, designated Rac13 and Rac9, respectively. The gene for Rac13 shows highly enhanced expression in developing cotton fibers, with maximal expression occurring at the time of transition between primary and secondary wall synthesis. This is also the time at which reorganization of the cytoskeleton occurs, and thus the pattern of expression of Rac13 is consistent with its possible role, analogous to animal Rac, in the signal transduction pathway that controls cytoskeletal organization.
Mol Gen Genet 1995 Jul 22
PMID:Genes encoding small GTP-binding proteins analogous to mammalian rac are preferentially expressed in developing cotton fibers. 765 26

We have cloned a novel cDNA (Spa-1) which is little expressed in the quiescent state but induced in the interleukin 2-stimulated cycling state of an interleukin 2-responsive murine lymphoid cell line by differential hybridization. Spa-1 mRNA (3.5 kb) was induced in normal lymphocytes following various types of mitogenic stimulation. In normal organs it is preferentially expressed in both fetal and adult lymphohematopoietic tissues. A Spa-1-encoded protein of 68 kDa is localized mostly in the nucleus. Its N-terminal domain is highly homologous to a human Rap1 GTPase-activating protein (GAP), and a fusion protein of this domain (SpanN) indeed exhibited GAP activity for Rap1/Rsr1 but not for Ras or Rho in vitro. Unlike the human Rap1 GAP, however, SpanN also exhibited GAP activity for Ran, so far the only known Ras-related GTPase in the nucleus. In the presence of serum, stable Spa-1 cDNA transfectants of NIH 3T3 cells (NIH/Spa-1) hardly overexpressed Spa-1 (p68), and they grew as normally as did the parental cells. When NIH/Spa-1 cells were serum starved to be arrested in the G1/G0 phase of the cell cycle, however, they, unlike the control cells, exhibited progressive Spa-1 p68 accumulation, and following the addition of serum they showed cell death resembling mitotic catastrophes of the S phase during cell cycle progression. The results indicate that the novel nuclear protein Spa-1, with a potentially active Ran GAP domain, severely hampers the mitogen-induced cell cycle progression when abnormally and/or prematurely expressed. Functions of the Spa-1 protein and its regulation are discussed in the context of its possible interaction with the Ran/RCC-1 system, which is involved in the coordinated nuclear functions, including cell division.
Mol Cell Biol 1995 Jan
PMID:Molecular cloning of a novel mitogen-inducible nuclear protein with a Ran GTPase-activating domain that affects cell cycle progression. 779 64

Scatter factor/hepatocyte growth factor (SF/HGF) stimulates the motility of epithelial cells, initially inducing centrifugal spreading of cell colonies followed by disruption of cell-cell junctions and subsequent cell scattering. These responses are accompanied by changes in the actin cytoskeleton, including increased membrane ruffling and lamellipodium extension, disappearance of peripheral actin bundles at the edges of colonies, and an overall decrease in stress fibers. The roles of the small GTP-binding proteins Ras, Rac, and Rho in regulating responses to SF/HGF were investigated by microinjection. Inhibition of endogenous Ras proteins prevented SF/HGF-induced actin reorganization, spreading, and scattering, whereas microinjection of activated H-Ras protein stimulated spreading and actin reorganization but not scattering. When a dominant inhibitor of Rac was injected, SF/HGF- and Ras-induced spreading and actin reorganization were prevented, although activated Rac alone did not stimulate either response. Microinjection of activated Rho inhibited spreading and scattering, while inhibition of Rho function led to the disappearance of stress fibers and peripheral bundles but did not prevent SF/HGF-induced motility. We conclude that Ras and Rac act downstream of the SF/HGF receptor p190Met to mediate cell spreading but that an additional signal is required to induce scattering.
Mol Cell Biol 1995 Feb
PMID:Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. 782 27

The exoenzyme C3 produced by Clostridium botulinum catalyzes ADP-ribosylation of rho gene products which belong to a family of small molecular-weight GTP-binding proteins. The C3 enzyme-catalyzed ADP-ribosylation of rho proteins partially purified from bovine brain was markedly activated by certain types of detergents or phospholipids and by endogenous factors present in the brain cytosol. Rho A protein that had been expressed in E. coli and subsequential purified was readily ADP-ribosylated by the C3 enzyme even in the absence of the activating factors. These results suggest that partially purified rho proteins contain an inhibitor, probably rho GDI (GDP-dissociation inhibitor for rho p21), of C3-catalyzed ADP-ribosylation. The activity of an endogenous enzyme, having the same substrate as botulinum C3 enzyme, was also found in brain cytosol. The enzyme activity was partially purified and characterized. The enzyme appeared to have a molecular mass of approximately 20,000 on a gel filtration and displayed unique properties similar to those observed with the botulinum C3 enzyme. The alpha-subunits of alpha beta gamma-trimeric G proteins which served as the substrates of cholera or pertussis toxin were not ADP-ribosylated by the brain enzyme.
Mol Cell Biochem 1994 Sep
PMID:Characterization of botulinum C3-catalyzed ADP-ribosylation of rho proteins and identification of mammalian C3-like ADP-ribosyltransferase. 789 56

The actin cytoskeleton appears to be as the cellular target of various clostridial ADP-ribosyltransferases which have been described during recent years. Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin and Clostridium spiroforme toxin ADP-ribosylate actin monomers and inhibit actin polymerization. Clostridium botulinum exoenzyme C3 and Clostridium limosum exoenzyme ADP-ribosylate the low-molecular-mass GTP-binding proteins of the Rho family, which participate in the regulation of the actin cytoskeleton. ADP-ribosylation inactivates the regulatory Rho proteins and disturbs the organization of the actin cytoskeleton.
Mol Cell Biochem 1994 Sep
PMID:Clostridial ADP-ribosylating toxins: effects on ATP and GTP-binding proteins. 789 61

Vav and Dbl are members of a novel class of oncogene proteins that share significant sequence identity in a approximately 250-amino-acid domain, designated the Dbl homology domain. Although Dbl functions as a guanine nucleotide exchange factor (GEF) and activator of Rho family proteins, recent evidence has demonstrated that Vav functions as a GEF for Ras proteins. Thus, transformation by Vav and Dbl may be a consequence of constitutive activation of Ras and Rho proteins, respectively. To address this possibility, we have compared the transforming activities of Vav and Dbl with that of the Ras GEF, GRF/CDC25. As expected, GRF-transformed cells exhibited the same reduction in actin stress fibers and focal adhesions as Ras-transformed cells. In contrast, Vav- and Dbl-transformed cells showed the same well-developed stress fibers and focal adhesions observed in normal or RhoA(63L)-transformed NIH 3T3 cells. Furthermore, neither Vav- or Dbl-transformed cells exhibited the elevated levels of Ras-GTP (60%) observed with GRF-transformed cells. Finally, GRF, but not Vav or Dbl, induced transcriptional activation from Ras-responsive DNA elements (ets/AP-1, fos promoter, and kappa B). However, like Ras- and GRF-transformed cells, both Vav- and Dbl-transformed cells exhibited constitutively activated mitogen-activated protein kinases (MAPKs) (primarily p42MAPK/ERK2). Since kinase-deficient forms of p42MAPK/ERK2 and p44MAPK/ERK1 inhibited Dbl transformation, MAPK activation may be an important component of its transforming activity. Taken together, our observations indicate that Vav and Dbl transformation is not a consequence of Ras activation and instead may involve the constitutive activation of MAPKs.
Mol Cell Biol 1994 Oct
PMID:Dbl and Vav mediate transformation via mitogen-activated protein kinase pathways that are distinct from those activated by oncogenic Ras. 793 2


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