Activation of serum response factor by RhoA is mediated by the nuclear factor-κB and C/EBP transcription factors

The activity of the transcription factor NF-kappa B can be modulated by members of the Rho family of small GT-Pases (Perona, R,, Montaner, S,, Saniger, L., Sanchez-Perez, I., Brave, R,, and Lacal, J. C, (1997) Genes Dev, 11, 463-475), Ectopic expression of RhoA, Rac1, and Cdc42Hs proteins induces the translocation of NF-kappa B dimers to the nucleus, triggering the transactivation of the NF-kappa B-dependent promoter from the human immunodeficiency virus. Here, we demonstrate that activation of NF-kappa B by RhoA does not exclusively promote its nuclear translocation and binding to the specific kappa B sequences, NF-kappa B is also involved in the regulation of the transcriptional activity of the c-fos serum response factor (SRF), since the activation of a SRE-dependent promoter by RhoA can be efficiently interfered by the double mutant I kappa B alpha S32A/S36A, an inhibitor of the NF-kappa B activity. We also present evidence that RelA. and p50 NF-kappa B subunits cooperate with the transcription factor C/EBP beta in the transactivation of the 4 x SRE-CAT reporter. Furthermore, RhoA increases the levels of C/EBP beta protein, facilitating the functional cooperation between NF-kappa B, C/EBP beta, and SRF proteins. These results strengthen the pivotal importance of the Rho family of small GTPases in signal transduction pathways which modulate gene expression and reveal that NF-kappa B and C/EBP beta transcription factors are accessory proteins for the RhoA-linked regulation of the activity of the SRF.