TY - JOUR
T1 - Functional Domains of Androgen Receptor Coactivator p44/Mep50/WDR77and Its Interaction with Smad1
AU - Li, Yirong
AU - Tian, Liantian
AU - Ligr, Martin
AU - Daniels, Garrett
AU - Peng, Yi
AU - Wu, Xinyu
AU - Singh, Mandeep
AU - Wei, Jianjun
AU - Shao, Yongzhao
AU - Lepor, Herbert
AU - Xu, Ruliang
AU - Chang, Zhijie
AU - Wang, Zhengxin
AU - Lee, Peng
N1 - Funding Information:
This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (Biomedical Laboratory Research and Development).
PY - 2013/5/29
Y1 - 2013/5/29
N2 - p44/MEP50/WDR77 has been identified as a coactivator of androgen receptor (AR), with distinct growth suppression and promotion function in gender specific endocrine organs and their malignancies. We dissected the functional domains of p44 for protein interaction with transcription factors, transcriptional activation, as well as the functional domains in p44 related to its growth inhibition in prostate cancer. Using a yeast two-hybrid screen, we identified a novel transcription complex AR-p44-Smad1, confirmed for physical interaction by co-immunoprecipitaion and functional interaction with luciferase assays in human prostate cancer cells. Yeast two-hybrid assay revealed that the N-terminal region of p44, instead of the traditional WD40 domain at the C-terminus, mediates the interaction among p44, N-terminus of AR and full length Smad1. Although both N and C terminal domains of p44 are necessary for maximum AR transcriptional activation, the N terminal fragment of p44 alone maintains the basic effect on AR transcriptional activation. Cell proliferation assays with N- and C- terminal deletion mutations indicated that the central portion of p44 is required for nuclear p44 mediated prostate cancer growth inhibition.
AB - p44/MEP50/WDR77 has been identified as a coactivator of androgen receptor (AR), with distinct growth suppression and promotion function in gender specific endocrine organs and their malignancies. We dissected the functional domains of p44 for protein interaction with transcription factors, transcriptional activation, as well as the functional domains in p44 related to its growth inhibition in prostate cancer. Using a yeast two-hybrid screen, we identified a novel transcription complex AR-p44-Smad1, confirmed for physical interaction by co-immunoprecipitaion and functional interaction with luciferase assays in human prostate cancer cells. Yeast two-hybrid assay revealed that the N-terminal region of p44, instead of the traditional WD40 domain at the C-terminus, mediates the interaction among p44, N-terminus of AR and full length Smad1. Although both N and C terminal domains of p44 are necessary for maximum AR transcriptional activation, the N terminal fragment of p44 alone maintains the basic effect on AR transcriptional activation. Cell proliferation assays with N- and C- terminal deletion mutations indicated that the central portion of p44 is required for nuclear p44 mediated prostate cancer growth inhibition.
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U2 - 10.1371/journal.pone.0064663
DO - 10.1371/journal.pone.0064663
M3 - Article
C2 - 23734213
AN - SCOPUS:84878448814
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 5
M1 - e64663
ER -