Strudwick S, Borden K L B
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York 10029, USA.
Leukemia. 2002 Oct;16(10):1906-17. doi: 10.1038/sj.leu.2402724.
In normal mammalian cells the promyelocytic leukemia protein (PML) is primarily localized in multiprotein nuclear complexes called PML nuclear bodies. However, both PML and PML nuclear bodies are disrupted in acute promyelocytic leukemia (APL). The treatment of APL patients with all-trans retinoic acid (ATRA) results in clinical remission associated with blast cell differentiation and reformation of the PML nuclear bodies. These observations imply that the structural integrity of the PML nuclear body is critically important for normal cellular functions. Indeed, PML protein is a negative growth regulator capable of causing growth arrest in the G(1) phase of the cell cycle, transformation suppression, senescence and apoptosis. These PML-mediated, physiological effects can be readily demonstrated. However, a discrete biochemical and molecular model of PML function has yet to be defined. Upon first assessment of the current PML literature there appears to be a seemingly endless list of potential PML partner proteins implicating PML in a variety of regulatory mechanisms at every level of gene expression. The purpose of this review is to simplify this confusing field of research by using strict criteria to deduce which models of PML body function are well supported.
在正常哺乳动物细胞中，早幼粒细胞白血病蛋白（PML）主要定位于称为PML核体的多蛋白核复合物中。然而，在急性早幼粒细胞白血病（APL）中，PML和PML核体均被破坏。用全反式维甲酸（ATRA）治疗APL患者可导致临床缓解，这与原始细胞分化和PML核体的重新形成有关。这些观察结果表明，PML核体的结构完整性对于正常细胞功能至关重要。实际上，PML蛋白是一种负性生长调节因子，能够在细胞周期的G(1)期引起生长停滞、抑制转化、诱导衰老和凋亡。这些由PML介导的生理效应很容易得到证实。然而，PML功能的具体生化和分子模型尚未明确。在首次评估当前关于PML的文献时，似乎有一长串潜在的PML伴侣蛋白，这表明PML参与了基因表达各个层面的多种调节机制。本综述的目的是通过使用严格的标准来推断哪些PML体功能模型得到了充分支持，从而简化这一令人困惑的研究领域。
