{Reference Type}: Journal Article
{Title}: Doxorubicin induces deglycosylation of cancer cell-intrinsic PD-1 by NGLY1.
{Author}: Wu D;Wu Z;Yao H;Yan X;Jiao Z;Liu Y;Zhang M;Wang D;
{Journal}: FEBS Lett
{Volume}: 598
{Issue}: 12
{Year}: 2024 Jun 23
{Factor}: 3.864
{DOI}: 10.1002/1873-3468.14935
{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.