Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body
Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body
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DOI：
10.1074/jbc.m707683200
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发表时间：
2008-02-29
影响因子：
4.8
通讯作者：
Kim, Hyun
中科院分区：
文献类型：
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作者：
Eun, Bokkee;Lee, Yool;Kim, Hyun
Hes6 是一种基本的螺旋-环-螺旋转录因子，在多能祖细胞的分化和肿瘤发生过程中发挥作用。然而，其功能的分子机制在很大程度上尚不清楚。在这里，我们证明 Hes6 是细胞核中早幼粒细胞白血病核体 (PML-NB) 复合物的组成部分，并且 Hes6 通过诱导 p21 细胞周期蛋白依赖性激酶抑制剂来抑制细胞增殖。我们进一步表明，Hes6 通过其基本结构域直接与 PML-NB 的关键成分之一 CREB 结合蛋白（CBP）相互作用。这种关联对于通过多种机制（包括染色质重塑和 p53 乙酰化）诱导 p21 至关重要。综上所述，这些结果表明 PML-NB 中的 Hes6-CBP 复合物可能通过 p53 依赖性和非依赖性途径影响细胞的增殖。
Hes6 is a basic helix-loop-helix transcription factor that functions in the differentiation of pluripotent progenitor cells and during tumorigenesis. However, the molecular mechanism for its function is largely unknown. Here we show that Hes6 is a component of the promyelocytic leukemia nuclear body (PML-NB) complex in the nuclei and that Hes6 inhibits cell proliferation through induction of p21 cyclin-dependent kinase inhibitor. We further show that Hes6 directly interacts with CREB-binding protein (CBP), one of the key components of PML-NB, via its basic domain. This association is critical for p21 induction through multiple mechanisms, including chromatin remodeling and p53 acetylation. Taken together, these results suggest that the Hes6-CBP complex in PML-NB may influence the proliferation of cells via p53-dependent and -independent pathways.