Question

1. How could DAPD1 loss-of-function explain what is seen in the patients?

2. Why would denaturation of the antigen before injection give the unexpected results described? Explain both why denaturation would lead to normal levels of T-cell response to virally infected cells, and lack of antibody binding to viral antigen.

Answer 1

1. Death-Associated Protein Kinase 1 (DAPK1) belongs to a family of five serine/threonine (Ser/Thr) kinases that possess tumor suppressive function and also mediate a wide range of cellular processes, including apoptosis and autophagy. DAPK1 is an important regulator of cell death and autophagy which act as a critical component in the ER stress-induced cell death pathway. It has been hypothesized that DAPK1 play a role in perinatal brain injury via the observation of highly expressed DAPK1 mRNA level in the developing brain. The loss -of–function of DAPK1 is associated with various cancer. DAPK1 is identified as a new component of the neuronal death signaling complex , which act as a signaling amplifier of N-methyl-D-aspartate (NMDA) receptors at extrasynaptic sites for mediating brain damage in stroke. DAPK1 has also been reported to mediate TNF-α and IFN-γ induced apoptosis as well as by activation of the Fas receptor. Although the relationship between cancer and autophagy is a complex and often contradictory one as during early stages, autophagy has a tumor suppressive function resulting from its ability to suppress accumulation of p62 and the generation of reactive oxygen species, and limit genomic instability in response to metabolic stress and oxidative stress.