Chlorpromazine induces cytotoxic autophagy in glioblastoma cells via endoplasmic reticulum stress and unfolded protein response

Table 1 GBM proteins identified as potential CPZ targets

Protein Name	Gene Name	UNIPROT Protein AC	Main Cellular Localization	Molecular function	Biological role in UPR
BiP	HSPA5	P11021	ER- Cytoplasm	Molecular chaperone	Master regulator of UPR [38,39,40]
Endoplasmin	HSP90B1	P14625	ER lumen	Molecular chaperone	Protein folding [41]; ER-associated degradation (ERAD) [42]
Heat shock protein HSP 90-beta	HSP90AB1	P08238	Cell membrane – Nucleus –Cytoplasm - Secreted	Molecular chaperone	Protein folding [43]
T-complex protein 1 (TRiC)	TCP1 (subunit alpha)	P17987	Cytoskeleton; cytosol	Subunits of chaperone complex TRiC	Protein folding [44, 45]
	CCT5 (subunit epsilon)	P48643	Cytoskeleton; cytoplasm
	CCT6 (subunit zeta)	P40227	Cytoplasm
	CCT8 (subunit theta)	P50990	Cytoskeleton - Cytoplasm
Heat shock protein 75 kDa	TRAP1	Q12931	Mitocondrion	Molecular chaperone	Translational attenuation [46]
Elongation factor 1-alpha 1	EEF1A1	P68104	Cell membrane - nucleus	Elongation factor	Regulation of chaperone-mediated autophagy [47]
EF2; Elongation factor 2	EEF2	P13639	Cytoplasm - Nucleus	Elongation factor	Inhibition of protein synthesis [48]
TER ATPase; Transitional endoplasmic reticulum ATPase	VCP	P55072	Cytosol; ER; nucleus	Hydrolase	Elimination of misfolded proteins from the ER [51]; ERAD pathway

GBM protein factors whose ability to bind ATP/GTP appeared modified by the presence of CPZ and thus recognized as potential targets of the drug. Their identification has been done via ABPP-MS, using a kinase enrichment procedure with an insoluble ATP probe

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