Bmi-1: At the crossroads of physiological and pathological biology.
Bmi-1: At the crossroads of physiological and pathological biology.
复制标题
DOI：
10.1016/j.gendis.2015.04.001
复制
发表时间：
2015-09
期刊：
影响因子：
6.8
通讯作者：
Dwivedi SK
中科院分区：
文献类型：
--
作者：
Bhattacharya R;Mustafi SB;Street M;Dey A;Dwivedi SK
Bmi-1是Polycomb阻遏复合物1的一员，通过调节染色质结构介导基因沉默，对正常和癌症干细胞的自我更新都必不可少。尽管三十年来的研究已经阐明了Bmi-1在调节DNA损伤反应、细胞生物能量学和病理方面的转录调控、翻译后修饰和功能，但具有如此多种功能的蛋白质的全部潜力仍有待实现。本文试图综合目前关于Bmi-1的知识，重点介绍其在正常生理和癌症中的作用。此外，由于癌症干细胞正在成为治疗耐药的新范例，因此也强调了Bmi-1在这方面的作用。广泛的恶性肿瘤暗示Bmi-1作为干细胞和肿瘤发生的标志，也使其成为治疗的合适候选者。尽管如此，迫切需要新的方法来进一步表征Bmi-1的生理作用，并将其作为预后标志物和治疗靶点的长期目标。
Bmi-1 is a member of the Polycomb repressor complex 1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells. Despite three decades of research that have elucidated the transcriptional regulation, post-translational modifications and functions of Bmi-1 in regulating the DNA damage response, cellular bioenergetics, and pathologies, the entire potential of a protein with such varied functions remains to be realized. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer. Additionally, since cancer stem cells are emerging as a new paradigm for therapy resistance, the role of Bmi-1 in this perspective is also highlighted. The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy. Nonetheless, new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target.