Ultraviolet-Induced Signal Trasduction

描述（由申请人提供）：本申请需要验证的假设是uvb诱导的c-Jun n末端激酶（JNKs）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变中起功能作用。因此，这些信号分子是开发化学预防剂来抑制uvb诱导的皮肤癌的潜在靶点。本应用的重点是鉴定和研究jnk的新底物及其在细胞转化/癌变中的生物学功能。

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.