Pinl regulates a subset of phosphoproteins by isomerizing Ser/Thr-Pro motifs via post-phosphorylation mechanisms.In our current study, we characterize TR3 as a novel Pin1 substrate.We show that (1) phosphorylation of TR3 by ERK facilitates the recognition and binding of Pinl;(2) TR3 Ser95 is the key site through which Pinl enhances TR3 stability by inhibiting its degradation;and (3) TR3 Ser431 is the isomerizing site of Pinl that activates TR3 transactivation by enhancing TR3 DNA binding.