Assuntos
Proteínas de Transporte/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Leucemia Mieloide Aguda/genética , Proteínas de Membrana/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína 1 Parceira de Translocação de RUNX1/metabolismo , Hormônios Tireóideos/genética , Translocação Genética , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Proteínas de Membrana/metabolismo , Camundongos , Mutação , Proteínas de Fusão Oncogênica/genética , Ligação Proteica , Proteína 1 Parceira de Translocação de RUNX1/genética , Elementos de Resposta , Hormônios Tireóideos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Ligação a Hormônio da TireoideRESUMO
The pyruvate kinase (PK) is a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, yielding one molecule of ATP. The M2 isoform of PK (PKM2) is predominantly expressed in normal proliferating cells and tumors, and both metabolic and non-metabolic activities for the enzyme in promoting tumor cell proliferation have been identified. However, the exact roles of PKM2 in tumor initiation, growth and maintenance are not yet fully understood. Using immunoprecipitation-coupled LC-MS/MS in MCF7 cells exposed to DNA-damaging agent, we report that the nuclear PKM2 interacts directly with P53 protein, a critical safeguard for genome stability. Specifically, PKM2 inhibits P53-dependent transactivation of the P21 gene by preventing P53 binding to the P21 promoter, leading to a nonstop G1 phase. As a result, PKM2 expression provides a growth advantage for tumor cells in the presence of a DNA damage stimulus. In addition, PKM2 interferes with phosphorylation of P53 at serine 15, known to stimulate P53 activity by the ATM serine/threonine kinase. These findings reveal a new role for PKM2 in modulating the DNA damage response and illustrate a novel mechanism of PKM2 participating in tumorigenesis.
Assuntos
Dano ao DNA , Neoplasias/metabolismo , Piruvato Quinase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Neoplasias/genética , Piruvato Quinase/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
By the method of hydroponic culture, and taking Cucurbita ficifolia B. as rootstock, this paper studied the effects of grafting on the root polyamine metabolism of cucumber seedlings under copper stress. The results showed that under copper stress, the root activities of cucumber seedlings were inhibited, and electrolyte leakage increased, with these changes being significantly lower for grafted than for ungrafted cucumber seedlings. In addition, the contents of free spermidine and spermine, and of conjugated and bound polyamines were significantly higher in grafted than in ungrafted seedling roots, while the free putrescine content and the ratio of free putrescine to polyamines were on the contrary. Comparing with those in ungrafted cucumber seedlings, the root arginine decarboxylase (ADC), ornithine decarboxylase (ODC), and S-adenosylmethionine decarboxylase (SAMDC) activities in grafted cucumber seedlings were higher, while the diamine oxidase and polyamine oxidase activities were significantly lower. All of these indicated that under copper stress, the synthesis of polyamine in grafted seedling roots was increased, while the degradation of polyamine was decreased, resulting in a higher accumulation of polyamine in the roots, and the increase of the tolerance of cucumber seedlings to copper stress.