2024-03-28T13:39:10Zhttps://www.tdx.cat/oai/requestoai:www.tdx.cat:10803/2834742024-03-15T10:57:28Zcom_10803_236col_10803_690278
00925njm 22002777a 4500
dc
Wierer, Michael
author
2013-01-13
Steroid receptors (SRs) are hormone-induced transcription factors that regulate gene expression by their concerted actions with coregulatory proteins. Performing a quantitative mass spectrometry-based interaction screen in breast cancer cells, we identified Polo-like kinase 1 to interact with progesterone receptor (PR) and estrogen receptor (ER) in presence of their respective hormone stimuli. PLK1 is recruited to chromatin and regulates SR-dependent and –independent gene transcription. Global gene expression analysis let us observe that PLK1-coactivated genes are enriched in developmental functions and linked to good clinical prognosis in breast cancer patients. Using large-scale phosphoproteomics with MCF7 breast cancer cells treated with estradiol in presence or absence of the specific PLK1 inhibitor BI2536, we observed that 28% of estradiol-induced phosphorylation sites depended on PLK1 activity. Among proteins with PLK1-dependent phosphorylation sites, we identified several transcriptional regulators including the ER-associated histone H3K4-methylase MLL2. As PLK1 inhibition reduced the estradiol-mediated induction of H3K4 methylation levels at MLL2 target genes, together these results propose a role of PLK1 in the regulation of MLL2 activity. Finally, in a targeted approach using recombinant histone proteins as substrate of PLK1, we observed a specific phosphorylation of histone H2B at serine 36. In summary, we conclude that PLK1 affects SR-dependent and SR-independent gene transcription by phosphorylating several transcriptional regulators and chromatin components.
http://hdl.handle.net/10803/283474
B 10131-2014
PLK1
Estrogen Receptor
Progesterone Receptor
Breast cancer
Phosphorylation
Gene transcription
MLL2
Phosphoproteomics
Interactomics
SILAC
Role of PLK1 in steroid hormone signaling in breast cancer cells