DIFFERENT MECHANISMS REGULATES DISC LARGE 1 PROTEIN LEVELS IN DIFFERENT BIOLOGICAL PROCESSES

MARZIALI FEDERICO; BUGNON VALDANO MARINA; ANA L. CAVATORTA; FACCIUTO FLORENCIA; GARDIOL DANIELA

Congreso; 50th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2014

Human Disc large (DLG1) has been demonstrated to be involved in the control of cell polarity and maintenance of tissue architecture. However, the mechanisms controlling DLG1 expression levels are poorly understood. This is relevant since DLG1 is lost in many tumours during the later stages of malignant progression. In this sense we initiated studies to analyse the mechanisms regulating DLG1 expression. We reported previously the discovery of an alternative splicing event in the 5? untranslated region (5´UTR) of DLG1 mRNA that generates two types of transcripts differing in their translation efficiency: the Short and Large 5´UTR variants. In this study, we further examined the impact of the DLG1 transcriptional rate and the role of the differential expression of the alternative 5´UTRs variants on DLG1 protein levels. We analyzed these mechanisms in cell processes like differentiation, cell cycle progression and cell-cell contacts, where the importance of DLG1 protein levels was previously established. Data presented here suggest that the transcriptional regulation of DLG1 strongly contributes to DLG1 abundance and show that differential expression of the alternative 5´UTRs variants also cooperates, depending on the cell type and cell situation. This study provides new evidence for understanding the mechanisms involved in DLG1 expression during different biological context