The use of phage display technique for the isolation of androgen receptor interacting peptides with (F/W)XXL(F/W) and FXXLY new signature motifs

Cheng Lung Hsu, Yuh Ling Chen, Shuyuan Yeh, Huei Ju Ting, Yueh Chiang Hu, Hank Lin, Xin Wang, Chawnshang Chang

研究成果: Article同行評審

73 引文 斯高帕斯(Scopus)

摘要

Early studies suggested that the signature motif, LXXLL, within steroid hormone receptor p160 coregulators may play important roles for the mediation of receptor-coregulator interaction. Interestingly, several androgen receptor (AR) coregulators, such as ARA70 and ARA55, may not use such a unique motif to mediate their coregulator activity. Here we apply the phage display technique to identify some new signature motifs, (F/W)XXL(F/W) and FXXLY (where F is phenylalanine, W is tryptophan, L is leucine, Y is tyrosine, and X is any amino acid) that can influence the interaction between AR and AR coregulators. Sequence analyses found that several AR coregulators, such as ARA70, ARA55, ARA54, and FHL2, contain FXXL(F/Y) motifs. Both glutathione S-transferase pull-down assays and transient transfection reporter assays demonstrate that these AR coregulators may use the FXXL(F/Y) motif to interact with AR and exert their AR coregulator activity. Exchanging the amino acid of Phe, Trp, or Tyr in this newly identified signature motif cluster may influence these peptides to interact with AR. The motif-containing peptides, as well as ARA70 of ARA54, may require selective flanking sequences for the better interaction with AR. In addition to influencing the AR transactivation, these motifs in AR-interacting peptides/proteins were also able to influence the AR N-/C-terminal interaction. Together, our data suggest that AR interacting peptides and/or AR coregulators may utilize the (F/W)XXL(F/W) and FXXLY motifs to mediate their interaction with AR and exert their influences on the AR transactivation.

原文English
頁(從 - 到)23691-23698
頁數8
期刊Journal of Biological Chemistry
278
發行號26
DOIs
出版狀態Published - 2003 七月 27

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子生物學
  • 細胞生物學

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