Regulation of serum response factor-driven transcription by MKL2 (megakaryoblastic leukemia 2) in response to BDNF

• Autorzy: Kalita K. , Rejmak E. , Kaczmarek L. , Hetman M.
• Języki publikacji: EN

Abstrakty

EN

SRF-mediated transcription contributes to brain plasticity. However, it is unclear which of the several SRF co-activators participates in transcriptional events underlying the formation and modifi cations of neuronal circuitries. We investigated the role of SRF co-activator, MKL2, in regulation of SRF-driven transcription in neurons. MKL2 expression was observed in newborn cortical or hippocampal neurons in culture as well as in adult rat forebrain. In-situ hybridization showed the presence of MKL2 mRNA in all fi elds of the hippocampus, especially in dentate gyrus. Neither overexpression nor inhibition of MKL2 by shRNA caused apoptotic cell death in neurons. Overexpression of MKL2 in primary cortical neurons enhanced SRF-driven transcription elevated by BDNF stimulation. In addition, inhibition of MKL2 reduced BDNF activation of SRF-driven transcription, on classical SRE promoters. MKL2 is a less potent activator of SRF-mediated transcription than recently studied member from the same family of co-activators MKL1. Interestingly, MKL2 is working as a partial inhibitor of BDNF activated MKL1-dependent transcription in case of promoters with isolated SRF binding sites. These results suggest that MKL2 contributes to BDNF-mediated regulation of SRF-driven gene expression. Particular mode of regulation depends on the presence of a second co-activator MKL1 or the type of SRF binding sites within the regulatory regions of respective genes. FNP Homing - MF EOG to KK, RO1 (NS047341-01) to MH.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.300

Twórcy

autor

Kalita K.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Rejmak E.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Kaczmarek L.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Hetman M.

• Kentucky Spinal Cord Injury Research Center and Department of Neurological Surgery, University of Louisville, Louisville, KY, USA