Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation DOI Creative Commons
Pei Yee Tey, Almut Dufner, Klaus‐Peter Knobeloch

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Abstract The immune checkpoint regulator CTLA4 is an unusually short-lived membrane protein. Here we show that its lysosomal degradation dependent on ubiquitylation at Lysine residues 203 and 213. Inhibition of the v-ATPase partially restores levels following cycloheximide treatment, but also reveals a fraction secreted in exosomes. endosomal deubiquitylase, USP8, interacts with loss enhances cancer cells, mouse CD4 + T cells cell-derived Depletion USP8 adapter protein, HD-PTP, not ESCRT-0 recapitulates this cellular phenotype, shows distinct properties vis-à-vis exosome incorporation. Re-expression wild-type neither catalytically inactive, nor localisation-compromised ΔMIT domain mutant can rescue delayed CTLA4, or counteract accumulation clustered endosomes. UbiCRest analysis CTLA4-associated ubiquitin chain linkages identifies complex mixture conventional Lys63- more unusual Lys27- Lys29-linked polyubiquitin chains may underly rapidity protein turnover.

Язык: Английский

Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose DOI Creative Commons
Daniel S. Bejan,

Rachel E. Lacoursiere,

Jonathan N. Pruneda

и другие.

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract The prevailing view on post-translational modifications (PTMs) is that a single amino acid modified with PTM at any given time. However, recent work has demonstrated crosstalk between different PTMs, some occurring the same residue. Such interplay seen ADP-ribosylation and ubiquitylation. For example, DELTEX E3 ligases were reported to ubiquitylate hydroxyl group free NAD + ADP-ribose in vitro, generating noncanonical ubiquitin ester-linked species. In this report, we show, for first time, dual occurs cells mono-ADP-ribosylated (MARylated) PARP10 Glu/Asp sites form MAR ester. We call process mono-ADP-ribosyl ubiquitylation or MARUbylation. Using chemical enzymatic treatments, including newly characterized bacterial deubiquitinase esterase-specific activity, discovered multiple PARPs are MARUbylated extended K11-linked polyubiquitin chains when exogenously expressed. Finally, show response type I interferon stimulation, MARUbylation can occur endogenously PARP targets. Thus, represents new broadens our understanding of function PARP-mediated cells.

Язык: Английский

Процитировано

3
Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation DOI Creative Commons
Pei Yee Tey, Almut Dufner, Klaus‐Peter Knobeloch

и другие.

The Journal of Cell Biology, Год журнала: 2024, Номер 224(1)

Опубликована: Сен. 28, 2024

The immune checkpoint regulator CTLA4 is an unusually short-lived membrane protein. Here, we show that its lysosomal degradation dependent on ubiquitylation at lysine residues 203 and 213. Inhibition of the v-ATPase partially restores levels following cycloheximide treatment, but also reveals a fraction secreted in exosomes. endosomal deubiquitylase, USP8, interacts with CTLA4, loss enhances cancer cells, mouse CD4+ T cell-derived Depletion USP8 adapter protein, HD-PTP, not ESCRT-0 recapitulates this cellular phenotype shows distinct properties vis-à-vis exosome incorporation. Re-expression wild-type neither catalytically inactive nor localization-compromised ΔMIT domain mutant can rescue delayed or counteract accumulation clustered endosomes. UbiCRest analysis CTLA4-associated ubiquitin chain linkages identifies complex mixture conventional Lys63- more unusual Lys27- Lys29-linked polyubiquitin chains may underly rapidity protein turnover.

Язык: Английский

Процитировано

2
Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation DOI Creative Commons
Pei Yee Tey, Almut Dufner, Klaus‐Peter Knobeloch

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Abstract The immune checkpoint regulator CTLA4 is an unusually short-lived membrane protein. Here we show that its lysosomal degradation dependent on ubiquitylation at Lysine residues 203 and 213. Inhibition of the v-ATPase partially restores levels following cycloheximide treatment, but also reveals a fraction secreted in exosomes. endosomal deubiquitylase, USP8, interacts with loss enhances cancer cells, mouse CD4 + T cells cell-derived Depletion USP8 adapter protein, HD-PTP, not ESCRT-0 recapitulates this cellular phenotype, shows distinct properties vis-à-vis exosome incorporation. Re-expression wild-type neither catalytically inactive, nor localisation-compromised ΔMIT domain mutant can rescue delayed CTLA4, or counteract accumulation clustered endosomes. UbiCRest analysis CTLA4-associated ubiquitin chain linkages identifies complex mixture conventional Lys63- more unusual Lys27- Lys29-linked polyubiquitin chains may underly rapidity protein turnover.

Язык: Английский

Процитировано

1