Browsing by Author "Barros, Patricia"
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- Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell-cycle-associated target gene promotersPublication . Barros, Patricia; Lam, Eric; Jordan, Peter; Matos, PauloGene expression depends on binding of transcriptional regulators to gene promoters, a process controlled by signalling pathways. The transcriptional repressor BCL-6downregulates genes involved in cell cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase activated protein kinase PAK1.Interestingly, the DNA motifs recognized by BCL-6 and STAT5 are similar. Because STAT5 stimulation in epithelial cells can also be triggered by Rac1 signalling, weasked whether both factors have opposing roles in transcriptional regulation and whether Rac1 signalling may coordinate a transcription factor switch. We usedchromatin immunoprecipitation to show that active Rac1 promotes release of the repressor BCL-6 while increasing binding of STAT5A to a BCL-6-regulated reportergene. We further show in colorectal cell lines that the endogenous activation status of the Rac1/PAK1 pathway correlated with the phosphorylation status of BCL-6and STAT5A. Three cellular genes (cyclin D2, p15INK4B, SUMO1) were identified to be inversely regulated by BCL-6 and STAT5A and responded to Rac1 signalling withincreased expression and corresponding changes in promoter occupancy. Together, our data show that Rac1 signalling controls a group of target genes that arerepressed by BCL-6 and activated by STAT5A, providing novel insights into the modulation of gene transcription by GTPase signalling.
- Stimulation of RAC1/PAK1 signalling upregulates DNA damage repair genes via STAT5 stimulation of BCL6 repressed lociPublication . Barros, Patricia; Amaral, Andreia; Abrantes, Leonor; Oliveira, Tiago; Louro, Henriqueta; Silva, Maria joão; Jordan, Peter; Gama-Carvalho, Margarida; Matos, PauloColorectal cancer is one of the most prevalent types of cancer worldwide. The GTPase RAC1 and its effector PAK1 have been found overexpressed or hyperactivated in colorectal cancers, particularly those with more aggressive and invasive features, leading to unfavourable clinical prognosis, often resulting from chemoresistance.
- Upregulation of RAC1/PAK1 signalling promotes DNA damage repair in colorectal cancer cellsPublication . Barros, Patricia; Amaral, Andreia; Abrantes, Leonor; Oliveira, Tiago; Louro, Henriqueta; Silva, Maria Joâo; Jordan, Peter; Gama Carvalho, Margarida; Matos, PauloIntroduction: Colorectal cancer is one of the most prevalent types of cancer worldwide. The GTPase RAC1 and its effector PAK1 have been found overexpressed or hyperactivated in this type of cancers, particularly those with more aggressive and invasive features, which is frequently correlated with resistance to chemotherapeutics and unfavourable clinical prognosis. Previously, we described a new signalling pathway in which activation of RAC1/PAK1 signalling promotes a transcriptional switch between the BCL6 repressor and the STAT5 transcriptional activator at a restricted subset of gene promoters.