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

The activity of the transcription factor NF-kappaB can be modulated by members of the Rho family of small GTPases (Perona, R., Montaner, S., Saniger, L., Sánchez-Pérez, I., Bravo, R., and Lacal, J. C. (1997) Genes Dev. 11, 463-475). Ectopic expression of RhoA, Rac1, and Cdc42Hs proteins induces the translocation of NF-kappaB dimers to the nucleus, triggering the transactivation of the NF-kappaB-dependent promoter from the human immunodeficiency virus. Here, we demonstrate that activation of NF-kappaB by RhoA does not exclusively promote its nuclear translocation and binding to the specific kappaB sequences. NF-kappaB 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 IkappaBalphaS32A/S36A, an inhibitor of the NF-kappaB activity. We also present evidence that RelA and p50 NF-kappaB subunits cooperate with the transcription factor C/EBPbeta in the transactivation of the 4 x SRE-CAT reporter. Furthermore, RhoA increases the levels of C/EBPbeta protein, facilitating the functional cooperation between NF-kappaB, C/EBPbeta, 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-kappaB and C/EBPbeta transcription factors are accessory proteins for the RhoA-linked regulation of the activity of the SRF.