Rac1 signalling modulates BCL-6-mediated repression of gene transcription

ITQB PhD Seminars

Title: Rac1 signalling modulates BCL-6-mediated repression of gene transcription

Speaker: Patrícia Barros

Laboratory: Glycobiology

Abstract

Rac1 is a member of the Rho family of small GTPases that regulates signalling pathways involved in cell adhesion and migration but also the regulation of gene transcription. Here we describe that the transcriptional repressor BCL-6 is regulated by Rac1 signalling. Transfection of active Rac1 mutants into colorectal DLD-1 cells led to increased expression of a BCL-6-controlled luciferase reporter construct. Conversely, inhibition of endogenous Rac1 activation by the Rac1 inhibitor NSC23766 decreased reporter activity. Moreover, BCL-6 lost its typical localization to nuclear dots upon activation of Rac1 and became predominantly soluble in a non-chromatin bound cell fraction. Rac1 signalling also regulated the expression of endogenous BCL-6-regulated genes, including the p50 precursor NF-kB1/p105 and the cell adhesion molecule CD44. Interestingly, these effects were not stimulated by the alternative splice variant Rac1b. The mechanism of BCL-6 inhibition does not involve formation of a stable Rac1/BCL-6 complex and is independent of Rac-induced ROS production or JNK activation. We show that PAK1 mediates the inhibition downstream of Rac and can directly phosphorylate Bcl-6. Together, these data provide substantial evidence that Rac1 signalling inhibits the transcriptional repressor BCL-6 in colorectal cells and reveal a novel pathway that links Rac1 signalling to the regulation of gene transcription.

Short-CV

2005/2006 Undergraduate training period at the Oncobiology laboratory of the Instituto Nacional de Saúde “Dr. Ricardo Jorge”, Lisboa, under the supervision of Dr. Paulo Matos and Dr. Peter Jordan.
2007 Degree in Biology – Scientific branch, Universidade de Évora.

Since 2007 PhD student working on The role of Rac1b-modulated gene transcription in tumorigenesis at the Department of Genetics of the Instituto Nacional de Saúde “Dr. Ricardo Jorge”, Lisboa, under the supervision of Dr. Peter Jordan.