REGULATION OF CYCLIN D1 EXPRESSION IN THE INTESTINE
肠道中细胞周期蛋白 D1 表达的调节
基本信息
- 批准号:6850662
- 负责人:
- 金额:$ 26.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-02-15 至 2007-01-31
- 项目状态:已结题
- 来源:
- 关键词:carcinogenesiscell growth regulationcell linecyclinsenzyme activityflow cytometrygastrointestinal epitheliumgreen fluorescent proteinsintestine neoplasmisozymeslaboratory mousemitogen activated protein kinaseneoplastic growthnuclear runoff assayposttranslational modificationsprotein kinase Cprotein protein interactiontissue /cell culture
项目摘要
DESCRIPTION (provided by applicant): Cyclin D1 is a tightly regulated cell
cycle control molecule that functions as a key determinant of progression
through G1 phase and as a major sensor of extracellular growth stimulatory and
inhibitory signals. Aberrant expression of cyclin D1 is one of the most
frequent abnormalities in human cancer, and is believed to play a causative
role in tumorigenesis. Understanding of the mechanisms underlying control of
cyclin D1 accumulation under normal and pathological conditions is, therefore,
of key importance. Based on preliminary data obtained using the intestinal
epithelium as a model system, strategies are proposed to test the hypothesis
that PKC signaling plays a critical role in regulating the expression of cyclin
D1 in intestinal epithelial cells and that disruption of PKC-mediated cyclin D1
control contributes to intestinal neoplasia. The following findings provide the
foundation for this hypothesis: (a) PKC activation in intestinal epithelial
cells leads to rapid downregulation of cyclin D1, via a novel glycogen synthase
kinase-3B independent and MAPK-dependent mechanism; (b) inhibition of PKC
isozyme activity/expression in intestinal cells is associated with marked
hyperinduction of cyclin D1 and increased cell growth; and (c) intestinal
adenomas and adenocarcinomas are frequently characterized by reduced/abrogated
PKC an expression and elevated levels of cyclin D1. To explore further the link
between PKC signaling and control of cyclin D1 accumulation in intestinal
cells, the following Specific Aims will be addressed: (1) Determine the
mechanisms underlying PKC-induced downregulation of cyclin D1; (2) understand
the mechanisms involved in cyclin D1 hyperinduction associated with loss of PKC
signaling; (3) identify the specific member(s) of the PKC family involved in
regulating cyclin D1 accumulation; (4) examine the signaling pathways involved
in PKC-related downmodulation and hyperinduction of cyclin D1; and (5) examine
the relationship between PKC a regulation of cyclin D1 expression and
tumorigenicity of intestinal cells.
描述(由申请人提供):细胞周期蛋白D1是一种严格调控的细胞
一种周期控制分子,作为疾病进展的关键决定因素
通过G1期,并作为细胞外生长刺激的主要传感器,
抑制信号细胞周期蛋白D1的异常表达是细胞周期中
在人类癌症中经常出现异常,并被认为是导致癌症的原因。
在肿瘤发生中的作用。了解控制疾病的基本机制
因此,在正常和病理条件下细胞周期蛋白D1的积累,
关键的重要性。根据使用肠道获得的初步数据,
上皮作为一个模型系统,提出了策略来检验假设
PKC信号在调节细胞周期蛋白的表达中起关键作用,
D1在肠上皮细胞中的表达及PKC介导的cyclin D1的破坏
控制有助于肠肿瘤形成。以下调查结果提供了
这一假设的基础:(a)PKC激活在肠上皮细胞
细胞导致细胞周期蛋白D1的快速下调,通过一种新的糖原合酶
激酶-3 B非依赖性和MAPK依赖性机制;(B)PKC抑制
肠细胞中的同工酶活性/表达与显著的
细胞周期蛋白D1的过度诱导和增加的细胞生长;和(c)肠
腺瘤和腺癌的特征通常是减少/消除
PKC表达和细胞周期蛋白D1水平升高。为了进一步探讨
PKC信号传导与细胞周期蛋白D1在肠上皮细胞中的积聚
细胞,将解决以下具体目标:(1)确定
PKC诱导细胞周期蛋白D1下调的机制;(2)了解
与PKC缺失相关的细胞周期蛋白D1过度诱导的机制
(3)识别参与信号传导的PKC家族的特定成员,
调节细胞周期蛋白D1的积累;(4)检查参与的信号通路
PKC相关下调和细胞周期蛋白D1的过度诱导;和(5)检查
蛋白激酶C α对细胞周期蛋白D1表达调控与细胞凋亡的关系
肠细胞的致瘤性。
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 }}
JENNIFER D. BLACK其他文献
JENNIFER D. BLACK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('JENNIFER D. BLACK', 18)}}的其他基金
Overcoming drug resistance using small molecule activators of protein phosphatase 2A
使用蛋白磷酸酶 2A 小分子激活剂克服耐药性
- 批准号:
10513191 - 财政年份:2022
- 资助金额:
$ 26.33万 - 项目类别:
Overcoming drug resistance using small molecule activators of protein phosphatase 2A
使用蛋白磷酸酶 2A 小分子激活剂克服耐药性
- 批准号:
10676204 - 财政年份:2022
- 资助金额:
$ 26.33万 - 项目类别:
Evaluating the PKC Enzyme System in Human Colon Cancer
评估人类结肠癌中的 PKC 酶系统
- 批准号:
9111892 - 财政年份:2015
- 资助金额:
$ 26.33万 - 项目类别:
Regulation of cyclin D1 expression in the intestine
肠道中细胞周期蛋白 D1 表达的调节
- 批准号:
8409912 - 财政年份:2002
- 资助金额:
$ 26.33万 - 项目类别:
Regulation of cyclin D1 expression in the intestine
肠道中细胞周期蛋白 D1 表达的调节
- 批准号:
7783589 - 财政年份:2002
- 资助金额:
$ 26.33万 - 项目类别:
Regulation of cyclin D1 expression in the intestine
肠道中细胞周期蛋白 D1 表达的调节
- 批准号:
8020046 - 财政年份:2002
- 资助金额:
$ 26.33万 - 项目类别:
REGULATION OF CYCLIN D1 EXPRESSION IN THE INTESTINE
肠道中细胞周期蛋白 D1 表达的调节
- 批准号:
6690370 - 财政年份:2002
- 资助金额:
$ 26.33万 - 项目类别:
Regulation of cyclin D1 expression in the intestine
肠道中细胞周期蛋白 D1 表达的调节
- 批准号:
8386908 - 财政年份:2002
- 资助金额:
$ 26.33万 - 项目类别:
REGULATION OF CYCLIN D1 EXPRESSION IN THE INTESTINE
肠道中细胞周期蛋白 D1 表达的调节
- 批准号:
6620564 - 财政年份:2002
- 资助金额:
$ 26.33万 - 项目类别:
相似海外基金
A novel mechanism of cell growth regulation by the intrinsically disordered protein, NPM1
内在无序蛋白 NPM1 调节细胞生长的新机制
- 批准号:
26440021 - 财政年份:2014
- 资助金额:
$ 26.33万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Study on the mechanism of cell growth regulation by ST2 and its possible anti-cancerous effect.
ST2调节细胞生长的机制及其可能的抗癌作用研究。
- 批准号:
25460393 - 财政年份:2013
- 资助金额:
$ 26.33万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular Mechanisms for cell growth regulation by Mnk-mediated translational control
Mnk 介导的翻译控制调节细胞生长的分子机制
- 批准号:
24590105 - 财政年份:2012
- 资助金额:
$ 26.33万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrating Phosphatidylcholine Metabolism with Cell Growth Regulation
将磷脂酰胆碱代谢与细胞生长调节相结合
- 批准号:
221878 - 财政年份:2010
- 资助金额:
$ 26.33万 - 项目类别:
Operating Grants
UNDERSTANDING THE ROLES OF SMALL GTPASES IN CELL GROWTH REGULATION
了解小 GTP 酶在细胞生长调节中的作用
- 批准号:
7955176 - 财政年份:2009
- 资助金额:
$ 26.33万 - 项目类别:
Roles of the Golgi apparatus in cell growth regulation
高尔基体在细胞生长调节中的作用
- 批准号:
18570173 - 财政年份:2006
- 资助金额:
$ 26.33万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanism of cell growth regulation by small G proteins
小G蛋白调节细胞生长的机制
- 批准号:
17014061 - 财政年份:2005
- 资助金额:
$ 26.33万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
The role of Kaiso in cell growth regulation
Kaiso 在细胞生长调节中的作用
- 批准号:
302718-2004 - 财政年份:2004
- 资助金额:
$ 26.33万 - 项目类别:
Postgraduate Scholarships - Master's
Bone Cell Growth Regulation by Runx2/Cbfa1
Runx2/Cbfa1 调节骨细胞生长
- 批准号:
6619987 - 财政年份:2003
- 资助金额:
$ 26.33万 - 项目类别:
Bone Cell Growth Regulation by Runx2/Cbfa1
Runx2/Cbfa1 调节骨细胞生长
- 批准号:
6898940 - 财政年份:2003
- 资助金额:
$ 26.33万 - 项目类别: