RESUMO
Glioma occurs due to multi-gene abnormalities. Neuropilin-1 (NRP-1), as a transmembrane protein, involves in glioma proliferation, invasion, and migration, as well as tumor angiogenesis. The cytoplasmic protein, GAIP/RGS19-interacting protein (GIPC1), could regulate the clathrin-vesicles trafficking and recycling. Here, we show that NRP-1 co-localizes and co-immunoprecipitates with GIPC1, and the C-terminal SEA-COOH motif of NRP-1 interacts specially with the named from three proteins: PSD-95 (a 95 kDa protein involved in signaling at the post-synaptic density), DLG (the Drosophila melanogaster Discs Large protein) and ZO-1 (the zonula occludens 1 protein involved in maintenance of epithelial polarity) (PDZ) domain of GIPC1 in glioma cells. Knockdown of GIPC1 by small interfering RNA (siRNA) significantly reduces the proliferation and invasion of glioma cells in vitro and increases its apoptosis. Furthermore, si-GIPC1 prevents the action of adaptor proteins adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1) and p130Cas and inhibits the downstream kirsten rat sarcoma viral oncogene homolog (KRAS)-ERK signaling pathway. This study demonstrated that NRP-1/GIPC1 pathway plays a vital role in glioma progression, and it is a potential important target for multi-gene combined therapeutics.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Glioma/patologia , Neuropilina-1/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Western Blotting , Movimento Celular , Proliferação de Células , Progressão da Doença , Citometria de Fluxo , Imunofluorescência , Glioma/metabolismo , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Invasividade Neoplásica , Ligação Proteica , RNA Interferente Pequeno/genética , Ratos , Transdução de Sinais , Células Tumorais CultivadasRESUMO
This paper has been retracted.
RESUMO
Bacterial persisters are phenotypic variants that tolerate exposure to lethal antibiotics. These dormant cells are responsible for chronic and recurrent infections. Multiple mechanisms have been linked to persister formation. Here, we report that a complex, consisting of an extracellular poly(dC) and its membrane-associated binding protein RmlB, appears to be associated with persistence of the opportunistic pathogen Pseudomonas aeruginosa. Environmental stimuli triggers a switch in the complex physiological state (from poly(dC)/RmlB to P-poly(dC)/RmlB or RmlB). In response to the switch, bacteria decrease proton motive force and intracellular ATP levels, forming dormant cells. This alteration in complex status is linked to a (p)ppGpp-controlled signaling pathway that includes inorganic polyphosphate, Lon protease, exonuclease VII (XseA/XseB), and the type III secretion system. The persistence might be also an adaptive response to the lethal action of the dTDP-L-rhamnose pathway shutdown, which occurs due to switching of poly(dC)/RmlB.