KRAB相关蛋白1(KRAB-associated protein 1,KAP1)又称转录中介因子1β(transcriptional intermediary factor 1β,TIF1β),也称三重基序蛋白28(tripartite motif-containing protein 28,TRIM28),是许多基因转录调控复合体中的支架分子,...KRAB相关蛋白1(KRAB-associated protein 1,KAP1)又称转录中介因子1β(transcriptional intermediary factor 1β,TIF1β),也称三重基序蛋白28(tripartite motif-containing protein 28,TRIM28),是许多基因转录调控复合体中的支架分子,参与免疫调节、胚胎早期发育、病毒复制、DNA损伤反应、肿瘤发生发展等许多生理病理过程的调控。KAP1存在磷酸化、乙酰化等多种翻译后修饰且参与蛋白质泛素化、类泛素化修饰和DNA甲基化、组蛋白甲基化、去乙酰化修饰,这对KAP1功能的发挥具有重要作用。该文综述了KAP1的功能及其在疾病中的研究进展,以期为KAP1相关疾病的分子治疗提供指导。展开更多
KAP1/TRIM28/TIF1β was identified nearly twenty years ago as a universal transcriptional co-repressor because it interacts with a large KRAB-containing zinc finger protein(KRAB-ZFP) transcription factor family. Many s...KAP1/TRIM28/TIF1β was identified nearly twenty years ago as a universal transcriptional co-repressor because it interacts with a large KRAB-containing zinc finger protein(KRAB-ZFP) transcription factor family. Many studies demonstrate that KAP1 affects gene expression by regulating the transcription of KRAB-ZFP-specific loci, trans-repressing as a transcriptional co-repressor or epigenetically modulating chromatin structure. Emerging evidence suggests that KAP1 also functions independent of gene regulation by serving as a SUMO/ubiquitin E3 ligase or signaling scaffold protein to mediate signal transduction. KAP1 is subjected to multiple post-translational modifications(PTMs), including serine/tyrosine phosphorylation, SUMOylation, and acetylation, which coordinately regulate KAP1 function and its protein abundance. KAP1 is involved in multiple aspects of cellular activities, including DNA damage response, virus replication, cytokine production and stem cell pluripotency. Moreover, knockout of KAP1 results in embryonic lethality, indicating that KAP1 is crucial for embryonic development and possibly impacts a wide-range of(patho)physiological manifestations. Indeed, studies from conditional knockout mouse models reveal that KAP1-deficiency significantly impairs vital physiological processes, such as immune maturation, stress vulnerability, hepatic metabolism, gamete development and erythropoiesis. In this review, we summarize and evaluate current literatures involving the biochemical and physiological functions of KAP1. In addition, increasing studies on the clinical relevance of KAP1 in cancer will also be discussed.展开更多
文摘KRAB相关蛋白1(KRAB-associated protein 1,KAP1)又称转录中介因子1β(transcriptional intermediary factor 1β,TIF1β),也称三重基序蛋白28(tripartite motif-containing protein 28,TRIM28),是许多基因转录调控复合体中的支架分子,参与免疫调节、胚胎早期发育、病毒复制、DNA损伤反应、肿瘤发生发展等许多生理病理过程的调控。KAP1存在磷酸化、乙酰化等多种翻译后修饰且参与蛋白质泛素化、类泛素化修饰和DNA甲基化、组蛋白甲基化、去乙酰化修饰,这对KAP1功能的发挥具有重要作用。该文综述了KAP1的功能及其在疾病中的研究进展,以期为KAP1相关疾病的分子治疗提供指导。
文摘KAP1/TRIM28/TIF1β was identified nearly twenty years ago as a universal transcriptional co-repressor because it interacts with a large KRAB-containing zinc finger protein(KRAB-ZFP) transcription factor family. Many studies demonstrate that KAP1 affects gene expression by regulating the transcription of KRAB-ZFP-specific loci, trans-repressing as a transcriptional co-repressor or epigenetically modulating chromatin structure. Emerging evidence suggests that KAP1 also functions independent of gene regulation by serving as a SUMO/ubiquitin E3 ligase or signaling scaffold protein to mediate signal transduction. KAP1 is subjected to multiple post-translational modifications(PTMs), including serine/tyrosine phosphorylation, SUMOylation, and acetylation, which coordinately regulate KAP1 function and its protein abundance. KAP1 is involved in multiple aspects of cellular activities, including DNA damage response, virus replication, cytokine production and stem cell pluripotency. Moreover, knockout of KAP1 results in embryonic lethality, indicating that KAP1 is crucial for embryonic development and possibly impacts a wide-range of(patho)physiological manifestations. Indeed, studies from conditional knockout mouse models reveal that KAP1-deficiency significantly impairs vital physiological processes, such as immune maturation, stress vulnerability, hepatic metabolism, gamete development and erythropoiesis. In this review, we summarize and evaluate current literatures involving the biochemical and physiological functions of KAP1. In addition, increasing studies on the clinical relevance of KAP1 in cancer will also be discussed.
