Details

Autor(en) / Beteiligte

• Saxena, Utsav H.
• Owens, Laura
• Graham, Julie R.
• Cooper, Geoffrey M.
• Hansen, Ulla

Titel

Prolyl Isomerase Pin1 Regulates Transcription Factor LSF (TFCP2) by Facilitating Dephosphorylation at Two Serine-Proline Motifs

Ist Teil von

• The Journal of biological chemistry, 2010-10, Vol.285 (41), p.31139-31147

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Transcription factor LSF is essential for cell cycle progression, being required for activating expression of the thymidylate synthase (Tyms) gene at the G1/S transition. We previously established that phosphorylation of LSF in early G1 at Ser-291 and Ser-309 inhibits its transcriptional activity and that dephosphorylation later in G1 is required for its reactivation. Here we reveal the role of prolyl cis-trans isomerase Pin1 in activating LSF, by facilitating dephosphorylation at both Ser-291 and Ser-309. We demonstrate that Pin1 binds LSF both in vitro and in vivo. Using coimmunoprecipitation assays, we identify three SP/TP motifs in LSF (at residues Ser-291, Ser-309, and Thr-329) that are required and sufficient for association with Pin1. Co-expression of Pin1 enhances LSF transactivation potential in reporter assays. The Pin1-dependent enhancement of LSF activity requires residue Thr-329 in LSF, requires both the WW and PPiase domains of Pin1, and correlates with hypophosphorylation of LSF at Ser-291 and Ser-309. These findings support a model in which the binding of Pin1 at the Thr-329—Pro-330 motif in LSF permits isomerization by Pin1 of the peptide bonds at the nearby phosphorylated SP motifs (Ser-291 and Ser-309) to the trans configuration, thereby facilitating their dephosphorylation.