Abstract

The present proposal is based on the hypothesis that androgen induces cellular responses via the activation of both gene expression and kinase cascade. The former is widely recognized, since the receptor for androgen itself is a transcriptional factor. The latter has begun to be appreciated in recent years, largely due to the realization that phosphorylation is an integral part for virtually all cellular processes. These two mechanisms however are not mutually exclusive, as transcriptional activation can lead to upregulation of kinases or phosphatases, thereby directly influencing the phosphorylatiion signaling. The present proposal is concerned with a novel serine kinase that is transcriptionally activated by androgen and that in turn regulates androgen receptor activity. It is generally overexpressed in prostate cancer cells, compared to normal counterpart. It is male-cell speciic and appears to be an integrator of signals coming from androgen and growth factor. There are three specific aims of the proposal: 1. To characterize MAK as a target of androgen activation. 1. To characterize MAK as a regulator of androgen receptor. 1. To characterize MAK as a modulator of androgen prostate cancer growth.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA114575-04
Application #
7395025
Study Section
Special Emphasis Panel (ZRG1-RUS-G (01))
Program Officer
Woodhouse, Elizabeth
Project Start
2005-06-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
4
Fiscal Year
2008
Total Cost
$224,441
Indirect Cost

  Institution

Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Shih, Jing-Wen; Chiang, Wei-Fan; Wu, Alexander T H et al. (2017) Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1? co-activator driving oral cancer progression. Nat Commun 8:15874
Wang, Ling-Yu; Hung, Chiu-Lien; Chen, Yun-Ru et al. (2016) KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis. Cell Rep 16:3016-3027
Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien et al. (2015) Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism. Int J Mol Sci 16:28943-78
Hung, Chiu-Lien; Wang, Ling-Yu; Yu, Yen-Ling et al. (2014) A long noncoding RNA connects c-Myc to tumor metabolism. Proc Natl Acad Sci U S A 111:18697-702
Wang, Hung-Jung; Hsieh, Ya-Ju; Cheng, Wen-Chi et al. (2014) JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1?-mediated glucose metabolism. Proc Natl Acad Sci U S A 111:279-84
Chang, Pei-Ching; Fitzgerald, Latricia D; Hsia, Datsun A et al. (2011) Histone demethylase JMJD2A regulates Kaposi's sarcoma-associated herpesvirus replication and is targeted by a viral transcriptional factor. J Virol 85:3283-93
Kung, Hsing-Jien (2011) Targeting tyrosine kinases and autophagy in prostate cancer. Horm Cancer 2:38-46
Wu, Zhaoju; Chang, Pei-Ching; Yang, Joy C et al. (2010) Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors. Genes Cancer 1:40-49
Hsia, Datsun A; Tepper, Clifford G; Pochampalli, Mamata R et al. (2010) KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation. Proc Natl Acad Sci U S A 107:9671-6
Chang, Pei-Ching; Izumiya, Yoshihiro; Wu, Chun-Yi et al. (2010) Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a SUMO E3 ligase that is SIM-dependent and SUMO-2/3-specific. J Biol Chem 285:5266-73

Showing the most recent 10 out of 20 publications