Control of CREB-binding protein signaling by nuclear fibroblast growth factor receptor-1 - A novel mechanism of gene regulation
Control of CREB-binding protein signaling by nuclear fibroblast growth factor receptor-1 - A novel mechanism of gene regulation
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DOI：
10.1074/jbc.m504400200
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发表时间：
2005-08-05
影响因子：
4.8
通讯作者：
Stachowiak, MK
中科院分区：
文献类型：
--
作者：
Fang, XH;Stachowiak, EK;Stachowiak, MK
在整合的核成纤维细胞生长因子受体-1（FGFR 1）信号转导中，新合成的FGFR 1易位到细胞核以刺激细胞分化和相关基因活性。目前的研究表明，FGFR 1积累和相互作用的转录共激活CREB结合蛋白（CBP）在核斑点域在发育中的大脑和神经祖细胞样细胞在体外，这伴随着分化和有丝分裂后的增长。细胞分化和核FGFR 1的基因激活不需要酪氨酸激酶活性。相反，FGFR 1通过增加RNA聚合酶II的募集和活性基因启动子处的组蛋白乙酰化来与CBP合作刺激转录。FGFR 1是一种多因子蛋白，其N端与CBP相互作用，C端与核糖体S6激酶1（RSK 1）相互作用。核FGFR 1通过1）从RSK 1抑制中释放CBP C端结构域和2）激活CBP N端结构域来增强CBP介导的转录。FGFR 1与CBP和RSK 1的相互作用允许基因转录的激活，并可能在细胞分化中发挥作用。
In integrative nuclear fibroblast growth factor receptor-1 ( FGFR1) signaling a newly synthesized FGFR1 translocates to the nucleus to stimulate cell differentiation and associated gene activities. The present study shows that FGFR1 accumulates and interacts with the transcriptional co-activator CREB-binding protein ( CBP) in nuclear speckle domains in the developing brain and in neural progenitor-like cells in vitro, which accompanies differentiation and postmitotic growth. Cell differentiation and gene activation by nuclear FGFR1 do not require tyrosine kinase activity. Instead, FGFR1 stimulates transcription in cooperation with CBP by increasing recruitment of RNA polymerase II and histone acetylation at the active gene promoter. FGFR1 is a multifactorial protein whose N terminus interacts with CBP and C terminus with ribosomal S6 kinase 1 ( RSK1). Nuclear FGFR1 augments CBP-mediated transcription by 1) releasing the CBP C-terminal domain from RSK1 inhibition and 2) activating the CBP N-terminal domain. The interaction of FGFR1 with CBP and RSK1 allows activation of gene transcription and may play a role in cell differentiation.