The molecular basis of the interaction between the proline-rich SH3-binding motif of PNRC and estrogen receptor alpha

Dujin Zhou, Jing Jing Ye, Yuping Li, Ki Lui, Shiuan Chen

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

PNRC and PNRC2 are members of a new family of nuclear receptor coactivators. We systematically determined the molecular basis and the structure/function relationship for the PNRC-ERα interaction. PNRC was found to interact with ERα mainly through its C-terminus region, amino acids 270-327, and an SH3-binding motif within this region was shown to be essential for PNRC to interact with and function as coactivator of ERα. The importance of the flanking sequences of SH3-binding motif in the interaction between PNRC and ERα was also investigated. The PNRC-interacting domain(s) on ERα was also mapped. PNRC was found to interact with both AF1 and LBD of ERα, and to function as a coactivator for both AF1 and AF2 transactivation functions. The interaction of ERα mutants, I358R, K362A, V376R, L539R and E542K, with PNRC/PNRC2 was further investigated. ERα/HBD/ V376R could bind to PNRC or PNRC2, with similar affinity as wild-type ERα/HBD, and the transactivation activity of ERα/V376R was enhanced 5-fold by PNRC. Since GRIP1, a well-characterized coactivator, was found not to be able to enhance the transactivation function of this mutant, our results indicate that the PNRC-ERα interaction interface is not exactly identical to that of GRIP1-ERα interaction.

Original languageEnglish
Pages (from-to)5974-5986
Number of pages13
JournalNucleic Acids Research
Volume34
Issue number20
DOIs
Publication statusPublished - Nov 2006

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