Phosphorylation stabilizes Nanog by promoting its interaction with Pin1
Phosphorylation stabilizes Nanog by promoting its interaction with Pin1
复制标题
DOI：
10.1073/pnas.1005847107
复制
发表时间：
2010-07-27
影响因子：
11.1
通讯作者：
Xu, Yang
中科院分区：
文献类型：
--
作者：
Moretto-Zita, Matteo;Jin, Hua;Xu, Yang
胚胎干细胞（ESCs）可以进行无限的自我更新，并保持多能性，分化为体内所有类型的细胞，因此作为人类治疗的可再生细胞来源具有很大的希望。维持ESCs自我更新的机制尚不清楚。在这里，我们表明，Nanog，一个转录因子的ESC的自我更新至关重要，是磷酸化在多个丝氨酸/苏氨酸-Pro基序。这种磷酸化促进Nanog和脯氨酰异构酶Pin 1之间的相互作用，通过抑制其泛素化导致Nanog稳定化。抑制胚胎干细胞中Pin 1活性或破坏Pin 1-Nanog相互作用会抑制其自我更新和在免疫缺陷小鼠中形成畸胎瘤的能力。因此，除了Nanog的严格转录调控外，Nanog的表达水平还受到翻译后机制的调节。
Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body, thus holding great promise as a renewable source of cells for human therapy. The mechanisms that maintain self-renewal of ESCs remain unclear. Here we show that Nanog, a transcription factor crucial for the self-renewal of ESCs, is phosphorylated at multiple Ser/Thr-Pro motifs. This phosphorylation promotes the interaction between Nanog and the prolyl isomerase Pin1, leading to Nanog stabilization by suppressing its ubiquitination. Inhibition of Pin1 activity or disruption of Pin1-Nanog interaction in ESCs suppresses their capability to self-renew and to form teratomas in immunodeficient mice. Therefore, in addition to the stringent transcriptional regulation of Nanog, the expression level of Nanog is also modulated by posttranslational mechanisms.