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- W3138304864 abstract "P97/VCP is a member of the AAA+ ATPase family that plays major roles in various cellular processes including control of protein homeostasis and chromatin-associated functions (transcription, replication, DNA damage, cellular cycle progression). Moreover, p97/VCP is involved in a growing number of diseases including cancers in which it has been shown to contribute to protein homeostasis and adaptation to oncogenic stresses. Indeed, p97/VCP expression is increased in numerous cancers and in some cases correlates with tumor recurrence and poor prognosis for patients. However, the precise mechanism by which p97/VCP regulates tumor cell proteostasis remains unclear. To address this, we demonstrated a role of p97/VCP in gene expression control upon endoplasmic reticulum (ER) stress. We found that in basal conditions, RuvBL2 is part of chromatin remodeler complex that included HDAC1 and mSin3A and act as a repressor of ER stress genes. However under ER stress, ubiquitinylated RuvBL2 is degraded by p97/VCP thus causing activation of ER stress genes. Moreover, we have identified GLI1, a known effector of Hedgehog signaling, as a target of the p97/VCP and RuvBL2-HDAC1-mSin3A complex. As a result under ER stress conditions, the Hedgehog pathway which have been linked to cancer development is non-canonically activated. Overall, our work indicated that p97/VCP acts as a molecular switch to inactivate RuvBL2-HDAC1 repressor complex under ER stress thus activating ER stress genes and Hedgehog genes in a non-canonical manner." @default.
- W3138304864 created "2021-03-29" @default.
- W3138304864 creator A5073167421 @default.
- W3138304864 date "2016-12-01" @default.
- W3138304864 modified "2023-09-25" @default.
- W3138304864 title "Epigenetic control of ER stress-mediated cellular reprogramming : role of the AAA+ ATPase p97/VCP" @default.
- W3138304864 hasPublicationYear "2016" @default.
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