染色质重塑是调控基因时序性表达的重要环节.衰老的人二倍体成纤维细胞核中有呈点状聚集的异染色质结构,这种特征性现象被称为衰老相关异染色质聚集(SAHF).K9M-H3和HP1是SAHF的标志性蛋白.在SAHF的形成过程中,p16INK4a/Rb途径和高迁移...染色质重塑是调控基因时序性表达的重要环节.衰老的人二倍体成纤维细胞核中有呈点状聚集的异染色质结构,这种特征性现象被称为衰老相关异染色质聚集(SAHF).K9M-H3和HP1是SAHF的标志性蛋白.在SAHF的形成过程中,p16INK4a/Rb途径和高迁移率蛋白A(high-mobility group A protein,HMGA protein)等许多因素起着非常重要的作用.最近研究表明,SAHF能够抑制E2F靶基因的表达,从而使细胞维持于稳定的衰老状态.SAHF的发现为细胞衰老的研究提供了一个新的生物学标志,并为细胞衰老状态的稳定维持提出了一种分子机制.展开更多
Cellular senescence is an irreversible form of cell cycle arrest that provides a barrier to neoplastic transformation. The integrity of the Rb （Retinoblastoma） pathway is necessary for the formation of the senescenc...Cellular senescence is an irreversible form of cell cycle arrest that provides a barrier to neoplastic transformation. The integrity of the Rb （Retinoblastoma） pathway is necessary for the formation of the senescence-associated heterochromatin foci （SAHF） that offers a molecular basis for the stability of the senescent state. Surprisingly, although high mobility group A2 protein （HMGA2） can promote tumorigenesis and inhibit Rb function in tumor cells, high-level expression of HMGA2 is sufficient to induce SAHF formation in primary cells. It therefore becomes significant to determine whether Rb protein is necessary in HMGA2-induced SAHF formation. In this study, we established the cellular senescence and SAHF assembly W138 cell model by ectopic expression of HMGA2, in which typical senescent markers were seen, including notable upregulation of p53, p21 and p16, and elevated SA-[3-galactosidase staining together with downregulation of E2F target genes. We then showed that the Rb pathway inhibitor E7 protein was able to partly abolish the ability of SAHF formation alter HMGA2 expression in W138 cells, indicating that Rb is a crucial factor for HMGA2-induced SAHF formation. However. Rb depletion did not completely rescue the cell growth arrest induced by HMGA2, suggesting that Rb is not an exclusive pathway for HMGA2-induced senescence in W138 cells.展开更多
文摘染色质重塑是调控基因时序性表达的重要环节.衰老的人二倍体成纤维细胞核中有呈点状聚集的异染色质结构,这种特征性现象被称为衰老相关异染色质聚集(SAHF).K9M-H3和HP1是SAHF的标志性蛋白.在SAHF的形成过程中,p16INK4a/Rb途径和高迁移率蛋白A(high-mobility group A protein,HMGA protein)等许多因素起着非常重要的作用.最近研究表明,SAHF能够抑制E2F靶基因的表达,从而使细胞维持于稳定的衰老状态.SAHF的发现为细胞衰老的研究提供了一个新的生物学标志,并为细胞衰老状态的稳定维持提出了一种分子机制.
基金supported by the grants from the National Natural Science Foundation of China(Nos.31100998 and 31050015)the Fundamental Research Funds for the Central Universities(No.11SSXT132)
文摘Cellular senescence is an irreversible form of cell cycle arrest that provides a barrier to neoplastic transformation. The integrity of the Rb （Retinoblastoma） pathway is necessary for the formation of the senescence-associated heterochromatin foci （SAHF） that offers a molecular basis for the stability of the senescent state. Surprisingly, although high mobility group A2 protein （HMGA2） can promote tumorigenesis and inhibit Rb function in tumor cells, high-level expression of HMGA2 is sufficient to induce SAHF formation in primary cells. It therefore becomes significant to determine whether Rb protein is necessary in HMGA2-induced SAHF formation. In this study, we established the cellular senescence and SAHF assembly W138 cell model by ectopic expression of HMGA2, in which typical senescent markers were seen, including notable upregulation of p53, p21 and p16, and elevated SA-[3-galactosidase staining together with downregulation of E2F target genes. We then showed that the Rb pathway inhibitor E7 protein was able to partly abolish the ability of SAHF formation alter HMGA2 expression in W138 cells, indicating that Rb is a crucial factor for HMGA2-induced SAHF formation. However. Rb depletion did not completely rescue the cell growth arrest induced by HMGA2, suggesting that Rb is not an exclusive pathway for HMGA2-induced senescence in W138 cells.
