G3BP1/2-Targeting PROTAC Disrupts Stress Granules Dependent ATF4 Migracytosis as Cancer Therapy DOI
Ting Dong, Fabao Zhao,

Mengmeng Wang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Stress granules (SGs) are membraneless cytoplasmic compartments that form in response to stress stimuli. In these compartments, most translation factors stall, except for activating transcription factor 4 (ATF4), which is preferentially translated ensure cell survival under stressful conditions. Cancer cells encounter various conditions the tumor microenvironment during tumorigenesis; however, how they exploit pro-survival effects of ATF4 SGs remains unclear. G3BP1/2 central nodes SG network, regulating dynamics. this study, we designed two small molecules, #129 and PROTAC (Proteolysis Targeting Chimera) degrader 129 (PT-129), specifically target NTF2L domain G3BP1/2, a crucial hub protein RNA interactions. These compounds inhibit formation stressed disassemble pre-existing granules. Furthermore, pharmacological inhibition by PT-129 suppressed fibroblast-mediated cancer growth vitro reduced vivo. Mechanistically, facilitates delivery from fibroblasts via migracytosis, primary mediator fibroblast-associated growth. PT-129-mediated disassembly disrupts delivery, thereby preventing proliferation. compounds, therefore, represent powerful tools gaining molecular insights into hold promise therapeutic interventions modulating granule

Language: Английский

HSF1 renders NK cells too stressed to respond DOI
Yael Gruper, Aviad Ben‐Shmuel, Ruth Scherz‐Shouval

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(10), P. 1630 - 1631

Published: Sept. 2, 2024

Language: Английский

Citations

0
G3BP1/2-Targeting PROTAC Disrupts Stress Granules Dependent ATF4 Migracytosis as Cancer Therapy DOI
Ting Dong, Fabao Zhao,

Mengmeng Wang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Stress granules (SGs) are membraneless cytoplasmic compartments that form in response to stress stimuli. In these compartments, most translation factors stall, except for activating transcription factor 4 (ATF4), which is preferentially translated ensure cell survival under stressful conditions. Cancer cells encounter various conditions the tumor microenvironment during tumorigenesis; however, how they exploit pro-survival effects of ATF4 SGs remains unclear. G3BP1/2 central nodes SG network, regulating dynamics. this study, we designed two small molecules, #129 and PROTAC (Proteolysis Targeting Chimera) degrader 129 (PT-129), specifically target NTF2L domain G3BP1/2, a crucial hub protein RNA interactions. These compounds inhibit formation stressed disassemble pre-existing granules. Furthermore, pharmacological inhibition by PT-129 suppressed fibroblast-mediated cancer growth vitro reduced vivo. Mechanistically, facilitates delivery from fibroblasts via migracytosis, primary mediator fibroblast-associated growth. PT-129-mediated disassembly disrupts delivery, thereby preventing proliferation. compounds, therefore, represent powerful tools gaining molecular insights into hold promise therapeutic interventions modulating granule

Language: Английский

Citations

0