Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ras-induced cell transformation is mediated through distinct downstream signaling pathways, including Raf, Ral-GEFs-, and phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathways. In some cell types, strong activation of the Ras-Raf-MEK-extracellular signal-regulated kinase (ERK) cascade leads to cell cycle arrest rather than cell division. We previously reported that constitutive activation of this pathway induces sustained proliferation of primary cultures of postmitotic chicken neuroretina (NR) cells. We used this model system to investigate the respective contributions of Ras downstream signaling pathways in Ras-induced cell proliferation. Three RasV12 mutants (S35, G37, and C40) which differ by their ability to bind to Ras effectors (Raf, Ral-GEFs, and the p110 subunit of PI 3-kinase, respectively) were able to induce sustained NR cell proliferation, although none of these mutants was reported to transform NIH 3T3 cells. Furthermore, they all repressed the promoter of QR1, a neuroretina growth arrest-specific gene. Overexpression of B-Raf or activated versions of Ras effectors Rlf-CAAX and p110-CAAX also induced NR cell division. The mitogenic effect of the RasC40-PI 3-kinase pathway appears to involve Rac and RhoA GTPases but not the antiapoptotic Akt (protein kinase B) signaling. Division induced by RasG37-Rlf appears to be independent of Ral GTPase activation and presumably requires an unidentified mechanism. Activation of either Ras downstream pathway resulted in ERK activation, and coexpression of a dominant negative MEK mutant or mKsr-1 kinase domain strongly inhibited proliferation induced by the three Ras mutants or by their effectors. Similar effects were observed with dominant negative mutants of Rac and Rho. Thus, both the Raf-MEK-ERK and Rac-Rho pathways are absolutely required for Ras-induced NR cell division. Activation of these two pathways by the three distinct Ras downstream effectors possibly relies on an autocrine or paracrine loop, implicating endogenous Ras, since the mitogenic effect of each Ras effector mutant was inhibited by RasN17.
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PMID:Induction of postmitotic neuroretina cell proliferation by distinct Ras downstream signaling pathways. 1098 23

Suaeda salsa is a leaf-succulent euhalophytic plant capable of surviving under seawater salinity. Here, we report the isolation and functional analysis of a novel Suaeda gene (designated as SsTypA1) encoding a member of the TypA/BipA GTPase gene family. The steady-state transcript level of SsTypA1 in S. salsa was up-regulated in response to various external stressors. Expression of SsTypA1 was restricted to the epidermal layers of the leaf and stem in S. salsa, and SsTypA1-green fluorescence protein (GFP) fusion proteins were targeted to the chloroplasts of tobacco leaves. Ectopic over-expression of SsTypA1 rendered the transgenic tobacco plants with significantly increased tolerance to oxidative stress, and this was accompanied by a reduction in H(2)O(2) content. Enzymatic and Western blot analyses revealed that the activity and amount of the thylakoid-bound NAD(P)H dehydrogenase (NDH) complex in the chloroplasts of leaf cells were enhanced. Additionally, an in vitro assay demonstrated that SsTypA1 bound to GTP and possessed GTPase activity that was stimulated by the presence of chloroplast 70S ribosomes. Together, these results suggest that SsTypA1 may play a critical role in the development of oxidative stress tolerance, perhaps as a translational regulator of the stress-responsive proteins involved in reactive oxygen species (ROS) suppression in chloroplast.
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PMID:SsTypA1, a chloroplast-specific TypA/BipA-type GTPase from the halophytic plant Suaeda salsa, plays a role in oxidative stress tolerance. 1837 22