Gabarap-KO Mouse

GABARAP, short for GABA type A receptor-associated protein, belongs to the LC3/GABARAP protein family evolved from yeast Atg8. It plays crucial roles in autophagy, a process maintaining cellular homeostasis by degrading and recycling aged and cytotoxic components. In autophagy, GABARAP is involved in steps like cargo recognition, vesicle closure, and trafficking. It also has functions in non-autophagy-related mechanisms [1].

Loss of GABARAP in multiple myeloma cells mediates resistance to immunogenic chemotherapy. Specifically, GABARAP deletion impairs the exposure of calreticulin (CRT) on dying cells, reducing phagocytosis by dendritic cells and the subsequent antitumor T-cell response. Low GABARAP levels are associated with shorter survival in patients and reduced tumor immune infiltration [2].

In conclusion, GABARAP is essential for autophagy-related and non-autophagy-related functions. In multiple myeloma, its loss-of-function significantly impacts the efficacy of immunogenic chemotherapy, highlighting its importance in understanding the disease mechanism and potentially developing new treatment strategies.