Rab1 GTPase regulates gene expression via p38 map kinase pathway

ROMERO, N.; *DUMUR, C. I.; SLAVIN, I.; MONETTA, P.; ALVAREZ, C. I .

Mar del Plata ,Bs.As., Argentina

Congreso; XLIII Reunión Anual Sociedad Argentina de Bioquimica y Biologia Molecular (SAIB); 2007

Sociedad Argentina de Bioquimica y Biologia Molecular (SAIB)

The GTPase Rab1 is essential for protein transport between the Endoplasmic Reticulum and the Golgi complex. In previous studies we have demonstrated that changes in Rab1 protein levels regulate gene expression of specific genes (among them KDELR3, GM130 and c-JUN) by modulating their gene promoter activity. In this work we aim to understand the molecular mechanism that can explain this Rab1-mediated function. Using a luciferase reporter assay, we show that changes in the previously mentioned gene promoter activity levels occurred at very short times after Rab1 induction. This data suggest that phosporylation events participate in these genes activation. To test if MAP kinase pathways participate in Rab1 induced response, specific pharmacological inhibitors of the p38, JNK and ERK MAP kinase pathways were used. Rab1-dependent activation was inhibited only by the p38 MAPK inhibitor. Furthermore, deletions of the 5ó-flanking regulatory region of KDELR3, GM130 shows that the consensus binding site for the transcription factor CREB (cAMP responsive element-binding protein) is required to response to Rab1changes. These results suggest that Rab1 modulates gene expression by activating the p38 MAPK signaling pathway and that CREB could be the transcription factor that response to this activation.