Genetic and Biochemical Analysis of MAB21 Proteins in Neuroblastoma Proliferation

Abstract

Neuroblastoma is the most prevalent and deadly form of childhood cancer with limited treatment options. To facilitate study of this rare disease and hundreds of others, we have developed a novel computational approach, known as URSAHD, that compares gene expression signatures of one disease to over 300 other diseases and normal tissues. The URSAHD neuroblastoma model identified MAB21L1 and MAB21L2 as unique to neuroblastoma. MAB21 proteins play a critical role in limb and nervous tissue development across animal models and humans, but there is no documented link between MAB21 proteins and neuroblastoma, nor is there clear evidence that MAB21 proteins have a catalytic function. Extending on preliminary results, this study finds that reduced levels of MAB21L1 and elevated levels of MAB21L2 both generate a growth defect. However, they do not interact in a synergistic manner, hinting that the MAB21 homologs do not impact growth together. Proteins assays reveal that native MAB21L1 and MAB21L2 preferentially localize in the nucleus and cytoplasm, respectively. In sum, our results suggest that MAB21L1 promotes cell growth in the nucleus and MAB21L2 perturbs cell growth in the cytoplasm. Notably, the MAB21L1 antibody cross-reacts with MAB21L2, revealing a way to measure MAB21L2 expression. Through this study, we offer the first in vivo functional assay for MAB21L1 and MAB21L2 in neuroblastoma cells, opening the door for deeper mechanistic and pathway-level analyses of these highly conserved proteins with great importance to human nervous system development and disease.