1: J Biol Chem. 1999 Mar 26;274(13):8506-15. 

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

Montaner S, Perona R, Saniger L, Lacal JC.

Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones
Cientificas, Madrid, Spain.

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.,
Sanchez-Perez, 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.

PMID: 10085083 [PubMed - indexed for MEDLINE]


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2: EMBO J. 1996 Jul 1;15(13):3403-12. 

Activation of the serum response factor by p65/NF-kappaB.

Franzoso G, Carlson L, Brown K, Daucher MB, Bressler P, Siebenlist U.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

This study demonstrates that the NF-kappaB subunit p65 can act like an accessory
protein for the serum response factor (SRF) in transfection assays. p65
functionally synergizes with SRF to activate the transcription of a reporter
construct dependent only on the serum response element (SRE). The synergy of the
two factors requires neither a kappaB motif nor direct contact of p65 with DNA.
Consistent with these results, a physical complex containing p65 and SRF is
observed in vitro. Synergy of the factors is independent of the previously
described activation domains present on p65, ruling out indirect effects of p65,
but synergy is dependent on the activation domain of SRF. The complexing of p65
and SRF is mediated by a segment of the SRF DNA binding domain, a region of the
protein which has also been reported to inhibit its own activation domain. We
speculate that p65, upon direct or facilitated interaction with SRF, may relieve
the inhibitory activity of this segment, thus enabling the activation domain of
SRF to become fully functional. In contrast to p65, the p50 subunit of NF-kappaB
does not interact significantly with SRF, either functionally or physically. The
data suggest the intriguing possibility that NF-kappaB may participate in the
regulation of SRE-dependent promoters, expanding the range of activities of this
rapidly activatable transcription factor.

PMID: 8670842 [PubMed - indexed for MEDLINE]


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