REGULATION OF DIFFERENTIATION IN LUNG AND EPIDERMAL KERATINOCYTES

肺和表皮角质形成细胞分化的调节

基本信息

项目摘要

Summary of Work: Squamous differentiation is a multi-stage process that occurs in many tissues. The molecular link between control of growth arrest and differentiation is being studied. Insight into these mechanisms are important not only for understanding the control of normal differentiation but also the defects in diseases such as squamous metaplasia and cancer. Several different signaling pathways can induce squamous differentiation including those initiated by interferon gamma and phorbol esters. We demonstrated that keratinocytes become growth arrested at a specific point in the G1 of the cell cycle and is accompanied by an inhibition of Rb phosphorylation, decrease in cdk activity and induction of the cdk-inhibitors p27, p21 and p16. Although ectopic expression of p21 or p27 causes growth arrest, cells do not differentiate suggesting that additional signals are involved in terminal differentiation. Carcinoma cells are resistant to terminal differentia- tion and changes in growth-regulatory genes and induction of squamous- specific genes were not observed. We have identified and cloned several genes that are regulated during squamous differentiation, including transglutaminase type I (TGase I) and a membrane protein CL-20/EMP-1. To study the transcriptional regulation of these genes, we cloned the upstream regulatory region of TGase I and CL20, and determined by footprinting, deletion mutation and mobility shift assays DNA elements that CREB/AP-1-like sites are important in their transcriptional control. The 2.9kb upstream regulatory region of the TGase I gene to control the expression of a chloramphenicol acetyltransferase (CAT) reporter gene was also analyzed in vivo. These studies showed that the -2.9 kb promoter region contains all the information for the proper issue- and differentiation-specific expression of TGase I.
工作总结:鳞状细胞分化是一种 在许多组织中发生的多阶段过程。分子链 控制生长停滞和分化之间的联系 研究了深入了解这些机制不仅对 了解正常分化的控制, 鳞状上皮化生和癌症等疾病的缺陷。几 不同的信号通路可以诱导鳞状细胞分化 包括由干扰素γ和佛波醇酯引发的那些。 我们证明,角质形成细胞生长停滞在 在细胞周期的G1中的特定点,并伴随着 抑制Rb磷酸化,降低cdk活性, 诱导CDK抑制剂p27、p21和p16。虽然异位 p21或p27的表达引起生长停滞,细胞不 差异表明,额外的信号参与了 终末分化癌细胞对终末 分化和生长调节基因的变化, 未观察到鳞状细胞特异性基因的诱导。我们有 鉴定并克隆了几个基因, 鳞状分化,包括转氨酶I型(TGase I)和膜蛋白CL-20/EMP-1。研究 这些基因的转录调控,我们克隆了上游 TGase I和CL 20的调节区,并通过 足迹法、缺失突变和迁移率变动分析 CREB/AP-1样位点在其表达中起重要作用。 转录调控2.9kb的上游调控区 控制氯霉素表达的TGase I基因 乙酰转移酶(CAT)报告基因也进行了体内分析。 这些研究表明,-2.9kb启动子区含有所有的 针对特定问题和独特优势的信息 TGase I的表达。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Anton M Jetten其他文献

化学物質と核内受容体:毒性評価・環境測定・創薬への展開
化学物质和核受体:毒性评估、环境测量和药物发现的进展
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hiroyuki Kojima;Yukimasa Takeda;Ryuta Muromoto;Miki Takahashi;Toru Hirao;Shinji Takeuchi;Anton M Jetten;and Tadashi Matsuda;小島弘幸
  • 通讯作者:
    小島弘幸
Promoting healthy aging. A 10-year community intervention for frailty prevention and its impact upon healthy aging in Japan
促进健康老龄化。
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hiroyuki Kojima;Yukimasa Takeda;Ryuta Muromoto;Miki Takahashi;Toru Hirao;Shinji Takeuchi;Anton M Jetten;and Tadashi Matsuda;Shinkai S
  • 通讯作者:
    Shinkai S
Vasodilatory properties of ghlerin in the rat
大鼠中ghlerin的血管舒张特性
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hiroyuki Kojima;Yukimasa Takeda;Ryuta Muromoto;Miki Takahashi;Toru Hirao;Shinji Takeuchi;Anton M Jetten;and Tadashi Matsuda;M. Ishido
  • 通讯作者:
    M. Ishido
In vitro endocrine-disrupting effects of pesticides via nuclear receptors.
农药通过核受体的体外内分泌干扰作用。
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hiroyuki Kojima;Yukimasa Takeda;Ryuta Muromoto;Miki Takahashi;Toru Hirao;Shinji Takeuchi;Anton M Jetten;and Tadashi Matsuda;小島弘幸;Hiroyuki Kojima
  • 通讯作者:
    Hiroyuki Kojima

Anton M Jetten的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Anton M Jetten', 18)}}的其他基金

REGULATION OF DIFFERENTIATION IN LUNG AND EPIDERMAL KERATINOCYTES
肺和表皮角质形成细胞分化的调节
  • 批准号:
    6289934
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Regulation Of Differentiation In Lung Keratinocytes
肺角质形成细胞分化的调节
  • 批准号:
    7007108
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Mechanism Of Action And Functions Of Glis 1-3
Glis的作用机制和功能1-3
  • 批准号:
    7007508
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Functions of PPAR in the lung
PPAR 在肺中的功能
  • 批准号:
    6673284
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Nuclear receptors: action, functions, and roles in disease
核受体:在疾病中的作用、功能和作用
  • 批准号:
    8734135
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Nuclear receptors: action, functions, and roles in disea
核受体:在疾病中的作用、功能和作用
  • 批准号:
    7327214
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Nuclear receptors: action, functions, and roles in disease
核受体:在疾病中的作用、功能和作用
  • 批准号:
    8336619
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Mechanism Of Action And Functions Of The Gli-related Proteins Glis 1-3
Gli相关蛋白Glis 1-3的作用机制和功能
  • 批准号:
    7968157
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Mechanism Of Action And Functions Of The Gli-related Proteins Glis 1-3
Gli相关蛋白Glis 1-3的作用机制和功能
  • 批准号:
    8149074
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Mechanism Of Action And Functions Of The Gli-related Pro
Gli相关Pro的作用机制和功能
  • 批准号:
    7170025
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

相似海外基金

ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
细胞粘附在生物信号转导中的作用
  • 批准号:
    6238317
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
细胞粘附在生物信号转导中的作用
  • 批准号:
    5210031
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
生物信号转导中的细胞粘附
  • 批准号:
    3732412
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了