Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077646-08
Application #
7172978
Study Section
Special Emphasis Panel (ZRG1-PTHB (03))
Program Officer
Okano, Paul
Project Start
1999-07-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
8
Fiscal Year
2007
Total Cost
$236,453
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Organized Research Units
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Jung, Sung Keun; Ha, Su Jeong; Jung, Chang Hwa et al. (2016) Naringenin targets ERK2 and suppresses UVB-induced photoaging. J Cell Mol Med 20:909-19
Kim, J-E; Roh, E; Lee, M H et al. (2016) Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis. Oncogene 35:4091-101
Bode, Ann M; Dong, Zigang (2015) Toxic phytochemicals and their potential risks for human cancer. Cancer Prev Res (Phila) 8:1-8
Wen, W; Peng, C; Kim, M O et al. (2014) Knockdown of RNF2 induces apoptosis by regulating MDM2 and p53 stability. Oncogene 33:421-8
Byun, Sanguine; Lee, Sung-Young; Lee, Jihoon et al. (2013) USP8 is a novel target for overcoming gefitinib resistance in lung cancer. Clin Cancer Res 19:3894-904
Cho, Yong-Yeon; Kim, Dong Joon; Lee, Hye Suk et al. (2013) Autophagy and cellular senescence mediated by Sox2 suppress malignancy of cancer cells. PLoS One 8:e57172
Song, Nu Ry; Lee, Eunjung; Byun, Sanguine et al. (2013) Isoangustone A, a novel licorice compound, inhibits cell proliferation by targeting PI3K, MKK4, and MKK7 in human melanoma. Cancer Prev Res (Phila) 6:1293-303
Liu, Kangdong; Yu, Donghoon; Cho, Yong-Yeon et al. (2013) Sunlight UV-induced skin cancer relies upon activation of the p38ýý signaling pathway. Cancer Res 73:2181-8
Bode, Ann M; Dong, Zigang (2013) Signal transduction and molecular targets of selected flavonoids. Antioxid Redox Signal 19:163-80
Zhang, J; Zhu, F; Li, X et al. (2012) Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation. Oncogene 31:1835-44

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