Doxorubicin induces deglycosylation of cancer cell-intrinsic PD-1 by NGLY1.
FEBS Lett
; 598(12): 1543-1553, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38782868
ABSTRACT
Tumor cells can express the immune checkpoint protein programmed death-1 (PD-1), but how cancer cell-intrinsic PD-1 is regulated in response to cellular stresses remains largely unknown. Here, we uncover a unique mechanism by which the chemotherapy drug doxorubicin (Dox) regulates cancer cell-intrinsic PD-1. Dox upregulates PD-1 mRNA while reducing PD-1 protein levels in tumor cells. Although Dox shortens the PD-1 half-life, it fails to directly induce PD-1 degradation. Instead, we observe that Dox promotes the interaction between peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (NGLY1) and PD-1, facilitating NGLY1-mediated PD-1 deglycosylation and destabilization. The maintenance of PD-1 sensitizes tumor cells to Dox-mediated antiproliferative effects. Our study unveils a regulatory mechanism of PD-1 in response to Dox and highlights a potential role of cancer cell-intrinsic PD-1 in Dox-mediated antitumor effects.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Doxorubicin
/
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
/
Programmed Cell Death 1 Receptor
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: