The proteasome participates in the activation of mbp promoter through the regulation of several transcription factors half life.

CALATAYUD C, PASQUINI J, SOTO E AND PASQUINI LA.

Cancun, México

Congreso; 21th Biennal Meeting. Internatioanal Society for Neurochemistry and American Society for Neurochemistry.; 2007

Internatioanal Society for Neurochemistry and American Society for Neurochemistry

  Our laboratory has demonstrated that the addition of low concentrations of lactacystin (L), a specific inhibitor of the proteasome (P), to oligodendroglial cell (OLGc) cultures, induces their differentiation. One important constituent of the myelin is MBP. The regulation of the mbp gene, which contains response elements to Sp1 that is regulated by the ubiquitin-P (Ub-P) system, takes place particularly at the beginning of transcription. We used an OLGc line (N20.1), transiently transfected with the MBP promoter and we observed, in the presence of L and MG132 (M), another P inhibitor, an increase in MBP promoter activity, in the levels of p27Kip1 and Sp1 and in the binding of Sp1 to its DNA sequence. To elucidate the MBP promoter region that was responding to P inhibition, we used another OLGc line (CG4), transiently transfected with different fragments of the MBP promoter. The highest activation was observed in the construct of the Sp1 region, suggesting that Sp1 is involved in the increased activity observed by L treatment and other factors that could be stabilized by the decreased P activity, could be repressing that activation. It has been shown that in CG4 cells, Sp1 competes for the binding to the same promoter region with Nkx2.2, an inhibitor which could also be a substrate of the P. We found that in CG4 cells, the expression of Sp1 was increased by L treatment while Nkx2.2 was increased by M treatment. Our results suggest that the UbPs seems to participate in the activation of the MBP promoter by stabilization of at least the two transcription factors mentioned above.