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Ultraviolet-Induced Signal Trasduction

紫外线诱导信号传导

基本信息

批准号：
6850690
负责人：
Zigang Dong
金额：
$ 24.94万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-07-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6850690
关键词：
JUN kinase apoptosis biological signal transduction carcinogenesis cell cycle cell transformation enzyme inhibitors genetically modified animals histones laboratory mouse mitogen activated protein kinase phosphorylation protein structure function skin neoplasms tissue /cell culture transcription factor tumor necrosis factor alpha ultraviolet radiation

项目摘要

DESCRIPTION (provided by applicant): The hypothesis to be tested in this application is that UVB-induced activation of c-Jun N-terminal kinases (JNKs) and their downstream transcription factors/nuclear proteins plays a functional role in UVB-induced cellular apoptosis and skin carcinogenesis. Therefore these signaling molecules are potential targets for the development of chemopreventive agents to inhibit UVB-induced skin cancers. The focus of this application is to identify and study novel substrates of JNKs and their biological functions in cell transformation/carcinogenesis. The specific aims to address this hypothesis are: Specific Aim 1. To determine the role of JNKs in UVB-induced phosphorylation of Statl and Stat3. Specific Aim 2. To determine the role of JNKs in UVB-induced phosphorylation of histones H3 and H2A. Specific Aim 3. To determine the role of JNKs, Statl, Stat3 and histones H3 and H2A in UVB- or TNFalpha-induced cell cycle arrest, apoptosis or cell transformation. Specific Aim 4. To determine the role of JNKs in UVB-induced skin carcinogenesis and their potential as targets for chemoprevention of skin cancer. Such knowledge will lead to a better understanding of human skin carcinogenesis, and facilitate the design of more effective agents for chemoprevention of human skin cancer.

描述（由申请人提供）：本申请中待检验的假设是，UVB诱导的c-Jun N-末端激酶（JNK）及其下游转录因子/核蛋白的激活在UVB诱导的细胞凋亡和皮肤癌发生中起功能性作用。因此，这些信号分子是开发化学预防剂以抑制UVB诱导的皮肤癌的潜在靶点。本申请的重点是鉴定和研究JNKs的新底物及其在细胞转化/致癌中的生物学功能。解决这一假设的具体目标是：具体目标1。为了确定JNK在UVB诱导的Statl和Stat 3磷酸化中的作用。具体目标2。探讨JNK在UVB诱导的组蛋白H3和H2 A磷酸化中的作用。具体目标3。确定JNK、Stat 1、Stat 3和组蛋白H3和H2 A在UVB或TNF α诱导的细胞周期停滞、凋亡或细胞转化中的作用。具体目标4。确定JNK在UVB诱导的皮肤癌发生中的作用及其作为皮肤癌化学预防靶点的潜力。这些知识将导致更好地了解人类皮肤癌的发生，并促进设计更有效的药物用于人类皮肤癌的化学预防。