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对称分裂与非对称分裂:两个协同激活因子的故事。

Symmetric division versus asymmetric division: a tale of two coactivators.

机构信息

University of Southern California, 1425 San Pablo Street, BCC-313, Los Angeles, CA 90033, USA.

出版信息

Future Med Chem. 2011 Oct;3(14):1745-63. doi: 10.4155/fmc.11.126.

Abstract

The decision for a stem cell to undergo a symmetric versus an asymmetric differentiation is probably the most critical cellular decision process in adults, as it probably underlies a large array of diseases, is associated with a decrease in tissue maintenance/homeostasis and the ability to repair properly, may mediate pathological processes such as cancer, fibrosis and neurodegeneration, and may be the underlying problem associated in general with aging. Interestingly and importantly, the decision to divide asymmetrically or symmetrically may be the major fundamental intrinsic difference between normal somatic stem and cancer stem cells. Based upon work done primarily in our laboratory over the past 10 years (both published and unpublished data), the article provides perspective on the critical importance of symmetric versus asymmetric divisions and the role of differential usage of the highly homologous coactivators Creb-binding protein (CBP) or p300 in the Wnt/catenin signaling cascade in stem cells and how they can be pharmacologically manipulated.

摘要

干细胞进行对称或不对称分化的决定可能是成体细胞中最关键的细胞决策过程,因为它可能是多种疾病的基础,与组织维持/体内平衡和正确修复能力的下降有关,可能介导癌症、纤维化和神经退行性变等病理过程,并且可能是与衰老相关的普遍存在的根本问题。有趣的是,重要的是,不对称或对称分裂的决定可能是正常体干细胞和癌症干细胞之间的主要内在基本差异。基于我们实验室在过去 10 年中所做的工作(已发表和未发表的数据),本文提供了关于对称与不对称分裂的关键重要性的观点,以及高度同源共激活因子 CBP 或 p300 在 Wnt/β-catenin 信号级联中的差异使用在干细胞中的作用,以及它们如何被药理学操纵。

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