Pin1 facilitates cancer proliferation by stabilizing phospho‐Sp1

Abstract

Sp1 is important for many gene transcriptions. How Sp1 is preserved in cancer cells during mitosis remains unknown. Here we found that Sp1 is phosphorylated at Thr739 by CDK1 before the entry of mitosis. Further, during mitosis, Pin1, a peptidyl‐prolyl isomerase, shields phospho‐Sp1‐Thr739 from dephosphorylation by PP2A via an action involving the isomerase activity of Pin1. Phospho‐Sp1 loses its affinity for DNA and appears to exist as a congregated ring in the periphery of chromosomes. At the end of mitosis and the beginning of interphase however, Sp1 becomes dephosphorylated by PP2A and returns to the chromatin. The results indicate that cancer cells utilize Pin1 to stabilize Sp1 in phosphorylated form and recycle the latter between mitosis and interphase. Pin1 thus, by stabilizing phospho‐Sp1, serves to facilitate the quick initiation and execution of interphase in order to maintain the favorable proliferative nature of cancer cells.