Role of Exon 0 in the Function of Mxi0

Background:
Neuroblastoma is the third most common childhood cancer. Unfortunately, despite intensive treatment, two-thirds of children with advanced neuroblastoma succumb to their disease. Current intensive therapies have significant side effects, so new treatment options must be developed. To do so requires a better understanding of how neuroblastoma cells survive despite these intensive therapies. N-Myc is a member of a family of proto-oncogenes (genes capable of leading to cancer development) implicated as a cause of several cancers. N-Myc plays a central role in the aggressiveness of neuroblastoma tumors.  Children whose neuroblastoma tumors have extra copies of the N-Myc gene (N-Myc amplification) fare worse than children whose tumors have the normal number of N-Myc genes. However, it is unknown why extra N-Myc leads to poor outcomes. Mxi1 is a transcription factor related to the Myc family of proteins, however, it counteracts the ability of N-Myc to cause cell growth and proliferation. We discovered a similar protein called Mxi0 that, unlike Mxi1, supports the ability of N-Myc to drive neuroblastoma growth. Mxi1 and Mxi0 are identical in structure except for one end of the protein. 

Project Goal:

In this proposal, we will test the hypothesis that the distinct segment of Mxi0 allows it to potentiate the actions of N-Myc in neuroblastoma rather than inhibiting it like Mxi1.  By understanding how Mxi0 works and what it does to support the function of N-Myc, we can hopefully identify targets that we can use to disrupt the function of N-Myc and make the neuroblastoma cells more sensitive to treatment.