PTPN23-dependent ESCRT machinery functions as a cell death checkpoint

Dongyan Song, Yuxin Cen, Zhe Qian, Xiaoli S. Wu, Keith Rivera, Tse-Luen Wee, Osama E. Demerdash, Kenneth Chang, Darryl Pappin, Christopher R. Vakoc and Nicholas K. Tonks ()
Additional contact information
Dongyan Song: Cold Spring Harbor
Yuxin Cen: Cold Spring Harbor
Zhe Qian: Cold Spring Harbor
Xiaoli S. Wu: Cold Spring Harbor
Keith Rivera: Cold Spring Harbor
Tse-Luen Wee: Cold Spring Harbor
Osama E. Demerdash: Cold Spring Harbor
Kenneth Chang: Cold Spring Harbor
Darryl Pappin: Cold Spring Harbor
Christopher R. Vakoc: Cold Spring Harbor
Nicholas K. Tonks: Cold Spring Harbor

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Cell death plasticity is crucial for modulating tissue homeostasis and immune responses, but our understanding of the molecular components that regulate cell death pathways to determine cell fate remains limited. Here, a CRISPR screen of acute myeloid leukemia cells identifies protein tyrosine phosphatase non-receptor type 23 (PTPN23) as essential for survival. Loss of PTPN23 activates nuclear factor-kappa B, apoptotic, necroptotic, and pyroptotic pathways by causing the accumulation of death receptors and toll-like receptors (TLRs) in endosomes. These effects are recapitulated by depletion of PTPN23 co-dependent genes in the endosomal sorting complex required for transport (ESCRT) pathway. Through proximity-dependent biotin labeling, we show that NAK-associated protein 1 interacts with PTPN23 to facilitate endosomal sorting of tumor necrosis factor receptor 1 (TNFR1), sensitizing cells to TNF-α-induced cytotoxicity. Our findings reveal PTPN23-dependent ESCRT machinery as a cell death checkpoint that regulates the spatiotemporal distribution of death receptors and TLRs to restrain multiple cell death pathways.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54749-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54749-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54749-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().