virginia magdalena mondaca rodriguez

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The Rockefeller University

University of Ulster

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Papers by virginia magdalena mondaca rodriguez

Retinoid receptor turnover mediated by sumoylation, ubiquitination and the valosin-containing protein is disrupted in glioblastoma

Scientific Reports, 2019

Resistance to therapeutic use of retinoids in glioma has been observed for over 20 years; however... more Resistance to therapeutic use of retinoids in glioma has been observed for over 20 years; however, the exact mechanism of resistance remains unknown. To understand retinoic acid resistance in glioma, we studied the turnover mechanism of retinoid receptor proteins in neural stem cells and glioma stem-like cells. Here, we show that in normal neural stem cells, proteasomal degradation of retinoid receptors involves sumoylation, ubiquitination and recognition by the valosin-containing protein (VCP/p97/Cdc48). We find that Sumo1 modification has a dual role to stabilize the retinoid receptor from unwanted degradation and signal additional modification via ubiquitination. Subsequently, the modified receptor binds to the VCP chaperone and both proteins are degraded by the proteasome. Additionally, we reveal that all trans retinoic acid (ATRA) induces VCP expression, creating a positive feedback loop that enhances degradation. In contrast, the pathway is impaired in the glioma stem-like cel...