PML: Regulation and multifaceted function beyond tumor suppression.
PML: Regulation and multifaceted function beyond tumor suppression.
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PML：超越肿瘤抑制的调节和多面功能。
DOI：
10.1186/s13578-018-0204-8
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发表时间：
2018
影响因子：
7.5
通讯作者：
Kao HY
中科院分区：
文献类型：
--
作者：
Hsu KS;Kao HY
早幼粒细胞白血病蛋白最初被认为是(15；17)染色体易位的急性早幼粒细胞白血病患者维甲酸受体α的融合伙伴，产生了早幼粒细胞白血病-RARα和RAR-α-早幼粒细胞白血病融合蛋白。大量证据表明，PML通过调节细胞凋亡、细胞周期、衰老和DNA损伤反应而具有肿瘤抑制活性。PML在哺乳动物细胞中富含离散的核亚基结构，直径0.2-1μm，又称Kremer小体、核区10、PML致癌结构域或PML核体(Nb)。PML-NB形成的失调会导致转录调控改变、蛋白质修饰、细胞凋亡和细胞衰老。除了PML NBS外，PML还存在于核质和细胞质中，包括内质网和线粒体相关膜。PML在肿瘤抑制中的作用已被广泛研究，但越来越多的证据表明，PML在干细胞更新、代谢、炎症反应、神经功能、乳腺发育和血管生成等方面也发挥着广泛的作用。在这篇综述中，我们将简要描述已知的PML的调节和功能，并包括新的发现。
Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML–RARα and RARα–PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2–1 μm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs). Dysregulation of PML NB formation results in altered transcriptional regulation, protein modification, apoptosis and cellular senescence. In addition to PML NBs, PML is also present in nucleoplasm and cytoplasmic compartments, including the endoplasmic reticulum and mitochondria-associated membranes. The role of PML in tumor suppression has been extensively studied but increasing evidence indicates that PML also plays versatile roles in stem cell renewal, metabolism, inflammatory responses, neural function, mammary development and angiogenesis. In this review, we will briefly describe the known PML regulation and function and include new findings.