Accession Number : ADA475797


Title :   The Role of Siah1-Induced Degradation of beta-Catenin in Androgen Receptor Signaling


Descriptive Note : Final rept. 15 Oct 2004-14 Oct 2007


Corporate Author : BURNHAM INST LA JOLLA CA


Personal Author(s) : Matsuzawa, Shu-ichi


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a475797.pdf


Report Date : Nov 2007


Pagination or Media Count : 27


Abstract : The androgen receptor (AR) signaling-pathway plays crucial roles in the growth and progression of prostate cancer cells. Recent studies indicate that beta-Catenin physically binds to AR and enhances its transcriptional activity in a ligand dependent manner. p53 has also been implicated in AR signaling because of its ability to induce expression of Siah1, which binds and activates E3 ligase complexes which degrade beta-Catenin. In this study, we demonstrated the biological significance and molecular mechanisms by which AR is regulated by the p53-induced Siah1 protein. Moreover, we identified the relevant proteins that are targeted for degradation by Siah1 besides beta-Catenin. Thus, enhanced Siah function may suppress the ability of androgen to promote tumor cell growth. Understanding more about the functions of Siah-family proteins may therefore suggest novel strategies for chemoprevention and for improved treatment of prostate cancer.


Descriptors :   *DEGRADATION , *PROTEINS , *ANDROGENS , *RECEPTOR SITES(PHYSIOLOGY) , SIGNALS , TRANSCRIPTION(GENETICS) , PROSTATE CANCER , LIGANDS , CELLS(BIOLOGY) , MOLECULAR PROPERTIES


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE