Pdcd6, also known as Programmed cell death protein 6, is an evolutionarily conserved Ca2+-binding protein. It is involved in regulating diverse cellular processes across different cellular compartments. Nuclear Pdcd6 regulates apoptosis and alternative splicing, while in the cytoplasm, it is required for coat protein complex II-dependent endoplasmic reticulum-to-Golgi apparatus vesicular transport, and is also involved in cytoskeletal dynamics and innate immune responses. Membranous Pdcd6 participates in membrane repair. Abnormal expression of Pdcd6 is closely associated with many diseases, especially cancer [1].

In a mouse model, Pdcd6 deficiency in mice and macrophages was found to induce enhanced bactericidal activity and LC3-associated phagocytosis (LAP) formation. Mechanistically, Pdcd6 interacts with lactate dehydrogenase A (LDHA) to downregulate lactate metabolism, affecting the lactylation of RUBCN and thus LAP formation and innate immune responses [2].

In conclusion, Pdcd6 plays crucial roles in multiple biological processes including apoptosis, vesicular transport, cytoskeletal dynamics, innate immune responses, and membrane repair. Mouse models with Pdcd6 deficiency have revealed its significance in antibacterial defense and LAP regulation, highlighting its potential as a target for infectious disease treatment. Additionally, its associations with various cancers suggest that further study of Pdcd6 could provide insights into cancer mechanisms and potential therapeutic strategies.

References:

1. Zhu, Yigao, Li, Qingchao. 2024. Multifaceted roles of PDCD6 both within and outside the cell. In Journal of cellular physiology, 239, e31235. doi:10.1002/jcp.31235. https://pubmed.ncbi.nlm.nih.gov/38436472/

2. Sun, Lulu, Wu, Sijin, Wang, Hui, Zhou, Jun, Li, Tianliang. 2024. PDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense. In Nature communications, 15, 10157. doi:10.1038/s41467-024-54377-w. https://pubmed.ncbi.nlm.nih.gov/39578445/