| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2040181 | Cell Reports | 2013 | 12 Pages |
•PLK1 acts as a transcriptional regulator during interphase in breast cancer cells•ER-dependent and ER-independent PLK1-coactivated genes have tumor-suppressive properties•A total of 28% of estradiol-induced phosphorylation events are mediated by PLK1•PLK1 mediates phosphorylation of various transcriptional coregulators
SummaryPolo-like kinase 1 (PLK1) is a key regulator of cell division and is overexpressed in many types of human cancers. Compared to its well-characterized role in mitosis, little is known about PLK1 functions in interphase. Here, we report that PLK1 mediates estrogen receptor (ER)-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. Performing large-scale phosphoproteomics of estradiol-treated MCF7 cells in the presence or absence of the specific PLK1 inhibitor BI2536, we identified several PLK1 end targets involved in transcription, including the histone H3K4 trimethylase MLL2, the function of which on ER target genes was impaired by PLK1 inhibition. Our results propose a mechanism for the tumor-suppressive role of PLK1 in mammals as an interphase transcriptional regulator.
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