CDK5RAP3 is activated by master TFs and regulates ER-Phagy in neuroblastoma

Cyclin-dependent kinase 5 regulatory subunit associated protein 3(CDK5RAP3) is regulated by master TFs in neuroblastoma, and its functions in neuroblastoma are yet unclear. Herein, we observed a significantly elevated CDK5RAP3 expression level in neuroblastoma, which was associated with a poor prognosis in patients. CDK5RAP3 promotes the growth of neuroblastoma cells both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interferes with UFMylation system, thereby triggering endoplasmic reticulum(ER)-Phagy. Additionally, we provide evidence that CDK5RAP3 maintains stability of MEIS2, a master TF in neuroblastoma, and in turn contributes high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms through which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy in neuroblastoma. Overall design: mRNA profiles of SK-N-BE(2) cells transfected with control shRNA (sh-NC) or sh-CDK5RAP3 were generated by RNA sequencing, in double, using Illumina NovaSeq6000.