Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/917
Título: Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters
Autor: Barros, Patrícia
Lam, Eric W-F
Jordan, Peter
Matos, Paulo
Palavras-chave: Vias de Transdução de Sinal e Patologias Associadas
Rac1
Gene Expression
STAT5
BCL-6
Chromatin Immunoprecipitation
Data: Jul-2012
Editora: Oxford University Press
Citação: Nucleic Acids Res. 2012 Sep 1;40(16):7776-87. Epub 2012 Jun 20.
Resumo: Gene expression depends on binding of transcriptional regulators to gene promoters, a process controlled by signalling pathways. The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates 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 signal transducers and activators of transcription 5 (STAT5) are similar. Because STAT5 stimulation in epithelial cells can also be triggered by Rac1 signalling, we asked whether both factors have opposing roles in transcriptional regulation and whether Rac1 signalling may coordinate a transcription factor switch. We used chromatin immunoprecipitation to show that active Rac1 promotes release of the repressor BCL-6 while increasing binding of STAT5A to a BCL-6-regulated reporter gene. We further show in colorectal cell lines that the endogenous activation status of the Rac1/PAK1 pathway correlated with the phosphorylation status of BCL-6 and STAT5A. Three cellular genes (cyclin D2, p15INK4B, small ubiquitin-like modifier 1) were identified to be inversely regulated by BCL-6 and STAT5A and responded to Rac1 signalling with increased expression and corresponding changes in promoter occupancy. Together, our data show that Rac1 signalling controls a group of target genes that are repressed by BCL-6 and activated by STAT5A, providing novel insights into the modulation of gene transcription by GTPase signalling.
Peer review: yes
URI: http://hdl.handle.net/10400.18/917
ISSN: 0305-1048
Versão do Editor: http://nar.oxfordjournals.org/content/early/2012/06/20/nar.gks571.long
Aparece nas colecções:DGH - Artigos em revistas internacionais

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