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Multiple monoubiquitination of Rtks is sufficient for their endocytosis and degradation

However, more recent evidence suggests that these vascular changes are not the cause of migraine, but rather an epiphenomenon that accompanies the pain (Rizzoli 2012)

This upregulation exhausts intracellular GSH, leading to ROS buildup and oxidative DNA damage that can ultimately generate TP53 mutations, a process that is halted when CHAC1 is knocked down ( TP53 induces ferroptosis primarily by transcriptionally repressing the expression of SLC7A11 ( TP53 lead to a loss of this repression, resulting in sustained SLC7A11 activity and greater cellular resistance to ferroptosis ( 3 KR, which cannot induce cell-cycle arrest, senescence or apoptosis, fully retains the ability to suppress SLC7A11 and trigger ferroptosis under oxidative stress ( The reasons for variable expression of CHAC1 in different cancers are still unclear, but it appears to be critically dependent on TP53 status

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