权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Cell cycle and differentiation of secretin-secreting enteroendocrine cells by transcription factor BETA2.

转录因子BETA2对促胰液素分泌肠内分泌细胞的细胞周期和分化。

基本信息

批准号：
12470126
负责人：
MUTOH Hiroyuki
金额：
$ 2.94万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470126/
关键词：
secretin gastrointestinal hormone differentiation growth transcription factor cell cycle cyclin cyclin dependent kinase

项目摘要

Expression of the hormone secretin in enteroendocrine cells is restricted to the nondividing villus compartment of the intestine, implying that terminal differentiation is linked to cell cycle arrest and that differentiation is repressed in actively proliferating cells. We have shown previously that the basic helix-loop-helix protein, BETA2/NeuroD, induces cell cycle withdrawal in addition to increasing secretin gene expression. A number of transcription factors important for differentiation are repressed by D cyclins. Repression by D cyclins appears to be independent of its effects on the cell cycle. We show that cyclin D1 represses BETA2/NeuroD-dependent transcription of the secretin gene. Examination of cyclin box mutants shows that repression is unrelated to Cdk4 activation. Although cyclin D1 and BETA2 associate in vivo, they do not directly interact. Cyclin D1 may be recruited to BETA2 by binding to the C-terminal domain of the p300 coactivator, downstream from the BETA2-binding site. In the small intestine, cyclin D1 expression occurs only in the actively proliferating crypts of Lieberkuhn but not in villi. Thus repression by cyclin D1 may serve to prevent secretin gene transcription from occurring in relatively immature epithelial progenitor cells.

肠内分泌细胞中激素促分泌素的表达仅限于肠的非分裂绒毛隔室，这意味着终末分化与细胞周期停滞有关，并且分化在活跃增殖的细胞中受到抑制。我们以前已经表明，基本的螺旋-环-螺旋蛋白，BETA 2/NeuroD，诱导细胞周期撤回除了增加分泌素基因表达。许多对分化重要的转录因子被D细胞周期蛋白抑制。D细胞周期蛋白的抑制作用似乎与其对细胞周期的影响无关。我们发现，细胞周期蛋白D1抑制分泌素基因的BETA2/NeuroD依赖性转录。细胞周期蛋白盒突变体的检查表明，镇压是无关的Cdk 4激活。虽然细胞周期蛋白D1和BETA 2在体内相关，但它们不直接相互作用。细胞周期蛋白D1可以通过与p300辅激活因子的C-末端结构域结合而被募集到BETA 2，该结构域位于BETA 2结合位点的下游。在小肠中，细胞周期蛋白D1的表达只发生在活跃增殖的Lieberkuhn隐窝，但不是在绒毛。因此，细胞周期蛋白D1的抑制可能有助于防止分泌素基因转录发生在相对不成熟的上皮祖细胞。