KRAB相关蛋白1(KRAB-associated protein 1,KAP1)是最早于1996年通过亲合色谱分离并克隆得到的一种转录辅因子,因能与含KRAB结构域的锌指蛋白家族(zinc family proteins,ZFPs)成员结合而得名。KAP1是一种具有多功能的蛋白质,它参与组蛋...KRAB相关蛋白1(KRAB-associated protein 1,KAP1)是最早于1996年通过亲合色谱分离并克隆得到的一种转录辅因子,因能与含KRAB结构域的锌指蛋白家族(zinc family proteins,ZFPs)成员结合而得名。KAP1是一种具有多功能的蛋白质,它参与组蛋白修饰与染色质重塑、调节DNA甲基化、作为转录共调控因子参与基因调控、参与DNA损伤反应等,并存在磷酸化、乙酰化等多种翻译后修饰。KAP1的表达水平与多种人类恶性肿瘤的发生发展密切相关,并影响肿瘤预后。因此,KAP1有望成为恶性肿瘤的诊断标志物或治疗新靶点。本文主要综述KAP1的结构、功能及其与人类恶性肿瘤发生发展的关系,并进一步探讨KAP1在恶性肿瘤研究中的应用前景,以期为恶性肿瘤的临床诊断和治疗提供参考依据。展开更多
PIG3 (p53-inducible gene 3), originally identified as one of a set of genes induced by p53 before the onset of apoptosis, was assumed to contribute to early cellular response to DNA damage. Here, we studied the relati...PIG3 (p53-inducible gene 3), originally identified as one of a set of genes induced by p53 before the onset of apoptosis, was assumed to contribute to early cellular response to DNA damage. Here, we studied the relation between p53 status and the increased expression of PIG3 by ionizing radiation (IR), and the related clues regarding the involvement of PIG3 in the cellular response to IR-induced DNA damage signaling. We demonstrated that the pentanucleotide microsatellite sequence was responsible for the p53-dependent induction of PIG3 transcription after irradiation, while sequence upstream of PIG3 promoter could maintain the basal level of expression which was not inducible by irradiation. The interaction of PIG3 and the KRAB-ZFP-associated protein 1 (KAP1), a DNA damage response protein, was revealed. PIG3 nucleus foci were formed 15 min after γ-ray irradiation, and which were found to partially colocalize with the phospho-KAP-1 foci as well as γ-H2AX foci. Although the lac operator tagged EGFP based reporter system revealed that PIG3 does not remodel chromatin in large scale in the cells under normal growing condition, it indeed prompted the chromatin relaxation in the cellular response to DNA damage signaling. All these data suggest that PIG3 is involved in IR-induced DNA damage response, and which maybe partially attribute to its interaction with KAP1.展开更多
试验旨在研究牦牛角蛋白关联蛋白1(keratin associated protein 1,KAP1)家族基因长度多态与重复序列特点。研究对牦牛和黄牛KAP1家族基因进行测序,并与绵羊已知序列进行比较分析。结果发现,牛KAP1家族位于19号染色体,根据绵羊KAP1家族...试验旨在研究牦牛角蛋白关联蛋白1(keratin associated protein 1,KAP1)家族基因长度多态与重复序列特点。研究对牦牛和黄牛KAP1家族基因进行测序,并与绵羊已知序列进行比较分析。结果发现,牛KAP1家族位于19号染色体,根据绵羊KAP1家族基因在染色体上的位置与相似性,重新命名了牛KAP1家族基因B2D、B2A、KAP1-1和B2C为KAP1-4、KAP1-1、KAP1-2、KAP1-3(按照染色体上的基因顺序)。KAP1家族基因之间在3′和5′端区域高度保守,中间有重复序列长度差异,其中牦牛KAP1-KAP4基因发现有30bp的长度多态。研究其蛋白序列发现5个氨基酸为基序的重复序列B(CCQTS)A1(CCQPT),以及一个新的重复序列C(SIQTS)。本研究结果说明重复序列是KAP1家族基因间和基因内的主要差异区域,这可能与其角蛋白结合螺旋数相关。展开更多
文摘KRAB相关蛋白1(KRAB-associated protein 1,KAP1)是最早于1996年通过亲合色谱分离并克隆得到的一种转录辅因子,因能与含KRAB结构域的锌指蛋白家族(zinc family proteins,ZFPs)成员结合而得名。KAP1是一种具有多功能的蛋白质,它参与组蛋白修饰与染色质重塑、调节DNA甲基化、作为转录共调控因子参与基因调控、参与DNA损伤反应等,并存在磷酸化、乙酰化等多种翻译后修饰。KAP1的表达水平与多种人类恶性肿瘤的发生发展密切相关,并影响肿瘤预后。因此,KAP1有望成为恶性肿瘤的诊断标志物或治疗新靶点。本文主要综述KAP1的结构、功能及其与人类恶性肿瘤发生发展的关系,并进一步探讨KAP1在恶性肿瘤研究中的应用前景,以期为恶性肿瘤的临床诊断和治疗提供参考依据。
基金supported by the National Basic Research Program of China (2007CB914603)the National Natural Science Foundation of China (30970677)the Outstanding Youth Scientist Foundation of National Natural Science Foundation of China (30825011)
文摘PIG3 (p53-inducible gene 3), originally identified as one of a set of genes induced by p53 before the onset of apoptosis, was assumed to contribute to early cellular response to DNA damage. Here, we studied the relation between p53 status and the increased expression of PIG3 by ionizing radiation (IR), and the related clues regarding the involvement of PIG3 in the cellular response to IR-induced DNA damage signaling. We demonstrated that the pentanucleotide microsatellite sequence was responsible for the p53-dependent induction of PIG3 transcription after irradiation, while sequence upstream of PIG3 promoter could maintain the basal level of expression which was not inducible by irradiation. The interaction of PIG3 and the KRAB-ZFP-associated protein 1 (KAP1), a DNA damage response protein, was revealed. PIG3 nucleus foci were formed 15 min after γ-ray irradiation, and which were found to partially colocalize with the phospho-KAP-1 foci as well as γ-H2AX foci. Although the lac operator tagged EGFP based reporter system revealed that PIG3 does not remodel chromatin in large scale in the cells under normal growing condition, it indeed prompted the chromatin relaxation in the cellular response to DNA damage signaling. All these data suggest that PIG3 is involved in IR-induced DNA damage response, and which maybe partially attribute to its interaction with KAP1.
文摘试验旨在研究牦牛角蛋白关联蛋白1(keratin associated protein 1,KAP1)家族基因长度多态与重复序列特点。研究对牦牛和黄牛KAP1家族基因进行测序,并与绵羊已知序列进行比较分析。结果发现,牛KAP1家族位于19号染色体,根据绵羊KAP1家族基因在染色体上的位置与相似性,重新命名了牛KAP1家族基因B2D、B2A、KAP1-1和B2C为KAP1-4、KAP1-1、KAP1-2、KAP1-3(按照染色体上的基因顺序)。KAP1家族基因之间在3′和5′端区域高度保守,中间有重复序列长度差异,其中牦牛KAP1-KAP4基因发现有30bp的长度多态。研究其蛋白序列发现5个氨基酸为基序的重复序列B(CCQTS)A1(CCQPT),以及一个新的重复序列C(SIQTS)。本研究结果说明重复序列是KAP1家族基因间和基因内的主要差异区域,这可能与其角蛋白结合螺旋数相关。
