RESUMO
The expression of the human Ras-GTPase activating protein (GAP)-binding protein (G3BP) was studied in human tumors and cell lines of different origins. Northern blot analysis and immunoblotting experiments showed enhanced expression of G3BP in all tumor samples as compared to healthy tissue. The enhanced expression does not seem to be related to the tumor site or to the stage of development of the cancer. In light of the proposed functions of G3BP, its increased expression in tumors suggest that it plays a role in dedifferentiation and proliferation processes. We also show that G3BP promotes S phase entry in cultured fibroblasts deprived of serum and that this function is dependent on the presence of the RNA binding domain of the protein.
Assuntos
Proteínas de Transporte/biossíntese , Neoplasias/metabolismo , Neoplasias/patologia , Fase S/fisiologia , Células 3T3/citologia , Células 3T3/metabolismo , Animais , Northern Blotting , Southern Blotting , Western Blotting , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , DNA Helicases , Progressão da Doença , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Camundongos , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/fisiologia , Transfecção , Células Tumorais CultivadasRESUMO
GM and KM immunoglobulin allotypes, which are the markers, respectively, of the constant parts of the heavy and the light chains of the IgG1, IgG2 and IgG3 subclasses, have been analysed in diabetic mellitus patients and controls living in New Caledonia. We tested 40 Europeans, 256 Melanesians and 44 Polynesians, as well as their 340 matched controls, in order to search for a genetic susceptibility at those polymorphic loci. All the subjects were tested for G1M (1, 2, 3, 17), G2M (23), G3M (5, 6, 10, 11, 13, 14, 15, 16, 21, 24, 28) and KM (1) by the classical hemagglutination method. The frequencies of GM haplotypes and KM alleles have been estimated by a maximum likelihood method. The results are in favour of no influence of the GM and KM loci. The prevalence of diabetes mellitus varies in the populations of New Caledonia: Polynesians are at much higher risk than Melanesians or Europeans. The GM haplotype distribution differs among ethnic groups; so they provide a useful marker to measure genetic admixture. The higher prevalence of diabetes observed among New Caledonians of European origin compared to the prevalence in Europe may be explained by genetic admixture with neighbouring Pacific populations, notably Polynesians (Asian haplotypes are present at a frequency of 9.4%). So, the genetic admixture should be measured in any genetic epidemiological study.
Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Alótipos de Imunoglobulina/genética , Alótipos Gm de Imunoglobulina/genética , Polimorfismo Genético , Adulto , População Negra , Estudos de Casos e Controles , Diversidade Cultural , Diabetes Mellitus Tipo 2/epidemiologia , Europa (Continente)/etnologia , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Haplótipos , Humanos , Funções Verossimilhança , Masculino , Programas de Rastreamento , Melanesia/etnologia , Pessoa de Meia-Idade , Nova Caledônia/epidemiologia , Polinésia/etnologia , Prevalência , População BrancaRESUMO
Sam68 is the major tyrosine-phosphorylated and Src-associated protein in mitotic cells. Sam68 stimulates G1/S transition and this effect is dependent on the integrity of its KH domain (hnRNPK Homology) which confers nucleic acid binding properties. During mitosis, Sam68 undergoes tyrosine phosphorylation, which negatively regulates its nucleic acid binding properties and mediates the interaction of Sam68 with critical SH2-containing signaling proteins such as Grb2, PLC gamma 1 and Ras-GAP. However, the interaction of Ras-GAP with Sam68 has been brought into question, based on the lack of co-immunoprecipitation between Sam68 and Ras-GAP in interphase cells. Here we show that the choice of anti-Ras-GAP antibodies is critical for the detection of Ras-GAP/Sam68 complex formation, and that this interaction is specific for G2/M transition in both NIH3T3 and Src-transformed cells. Such data reinforce the importance of the interaction of Ras-GAP with RNA binding proteins during cell proliferation through its SH2 and SH3 domains.