Nrdp1s, Short Variant Of Nrdp1, Inhibits Human Glioma Progression By Increasing Nrdp1-Mediated Erbb3 Ubiquitination And Degradation

The ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp1) is involved in the induction of apoptosis and suppression of tumour formation. We previously showed that it was expressed at lower levels in human glioma tissues compared with normal brain tissues. However, the mechanism underlying this is unclear. Here, we reported that a novel short variant (Nrdp1S), lacking 71 amino acids at the N-terminal, was expressed in normal human brain tissue, but absent from glioma tissues. Similar to Nrdp1, Nrdp1S could be degraded by the proteasomal pathway, but exhibited an even longer half-life than Nrdp1. Nrdp1S was also shown to form a heterodimer with Nrdp1, which increased its stability, thereby augmenting the Nrdp1-mediated ubiquitination and degradation of ErbB3. EdU incorporation, MTT assay and in vitro colony formation demonstrated that Nrdp1S significantly inhibited the cell tumourigenicity. These results together suggest that Nrdp1S is a tumour suppressor that which potentiates the Nrdp1-mediated ubiquitination and degradation of ErbB3. An Nrdp1S deficiency may also be an important factor in the loss of Nrdp1.