Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery

Second international symposium on the chaperone code, 2023

“…Atg1/Ulk1-mediated phosphorylation of Hsp90 leads to dissociation of the Hsp90:Atg1/Ulk1 complex and activation of Atg1/Ulk1, which is essential for initiation of autophagy. 13 This work indicates a reciprocal regulatory mechanism between the chaperone Hsp90 and the autophagy kinase Atg1/Ulk1 and consequent maintenance of cellular proteostasis. Jill Johnson (University of Idaho, USA) discussed new results that take advantage of mutations in yeast Hsp90 that disrupt different steps within the folding pathway.…”

Insights into Hsp90 mechanism and in vivo functions learned from studies in the yeast, Saccharomyces cerevisiae

“…Interestingly, phosphorylation of T22 decreases binding of Cdc37, while phosphorylation of T101 has been found to increase interaction with Cdc37 ( Mollapour et al, 2011 ; Woodford et al, 2016 ). Another recently identified temperature-sensitive mutation, S25P, also occurs at a residue in the amino-terminus known to undergo phorphorylation ( Mercier et al, 2019 ; Backe et al, 2023b ). SUMOylation and tyrosine phosphorylation of Hsp90 residues have also been shown to affect Hsp90 function ( Mollapour et al, 2010 ; Xu et al, 2012 ; Beebe et al, 2013 ; Mollapour et al, 2014 ).…”

Exploiting Nanotechnology for Drug Delivery: Advancing the Anti-Cancer Effects of Autophagy-Modulating Compounds in Traditional Chinese Medicine

“…The following Table 1 summarizes the autophagy-modulating ingredients of TCM and their nanoformulations. EVO and CQ-loaded liposomes [169] FA-targeted EVO-loaded nano-micelles [170] TPP-targeted Dex-ss-SPCL NPs load DOX and EVO [171] pH-triggered EVO-loaded DUCNPs with in vivo tumour imaging function [172] EGFR-targeted EVO-loaded NCA NPs with in vivo tumour imaging function [173] Icariin PI3K/AKT/mTOR miR-7/mTOR/ SREBP1 [108,110] AEAA-targeted ICA-loaded PLGA-PEG NPs with ICD-induced function [147] ICA and pyropheophorbide-a self-assembled NPs combining ROS-induced, autophagy-induced, and PDT function [174] Thermosensitive liposome loading ICA [148] iRGD-modified ICA-loaded DSPE-PEG NPs encapsulated by RBC membrane [175] Luteolin SGK1/FOXO3a/ BNIP3 PI3K/AKT/mTOR [116,176] FA-targeted LUT-loaded PEG-PCL NPs [149] ROS-triggered LUT-loaded PPS-PEG NPs [177] ROS-triggered and FA-targeted loaded LUT DSPE-PEG NPs [178] Epigallocatechin gallate PI3K/AKT/mTOR JAK/STAT3 Ras/MEK/ERK HSP90 related pathways [117,[119][120][121]179,180] HA-targeted EGCG NPs with ROS-induced and ferroptosis-induced function [181] Manganese carbonyl and dendritic mesoporous silicon NPs loading EGCG with PTT function [182] PD-L1 targeted fluorinated-coordinative-EGCG loaded Zn2+ NPs [183] FA-targeted EGCG-loaded liposomes [184] UV blocker ZnO and the antioxidants lycopene and olive oil copolymer NPs loaded EGCG [185] α SKN and CQ-loaded liposomes combining autophagy-induced and ICD-induced function [58] Fe-Shikonin metal-phenolic networks covering CpG ODN-loaded aluminum hydroxyphosphate nanoparticles loading SKN as in situ nano vaccines inducing ICD, ferroptosis, and necroptosis [191] Transferrin-targeted SKN and JQ1 loaded with ICD-induced function [192] (Continued)…”

“…182 Considering the established correlation between HSP90 and autophagy, it would be intriguing to investigate whether autophagy plays a more direct role in tumor treatment when utilizing these nanodrugs. 179 Furthermore, extensive research has been conducted on a nano-delivery system employing inorganic zinc as a carrier for loading EGCG. 183 Similarly, the development of EGCG-loaded liposomes incorporating FA has been pursued for the targeted treatment of colon cancer.…”