Determining the Function of ALTO, a Novel Protein of Merkel Cell Polyomavirus

Abstract

Merkel Cell Polyomavirus (MCPyV) was discovered clonally integrated in a rare skin cancer called Merkel Cell Carcinoma (MCC). Our group recently showed that MCPyV has a novel gene named Alternative to Large T Open reading frame (ALTO). ALTO’s function is unknown. ALTO is not an oncogene but it is related to Middle T antigen (MT), the main oncogene of the well-studied Murine Polyomavirus (MuPyV). ALTO and MT have a conserved membrane anchor and an adjacent basic amino acid motif. These domains allow MT to associate with membrane cytoskeleton and to localize with cellular interactors. ALTO also has tyrosine motifs that resemble those of MT. For MT these tyrosines are docking sites for cellular interactors. However, ALTO and MT are very divergent. We used affinity-purification mass spectrometry to identify ALTO’s binding partners. We tested the effect of ALTO on the activities its interactors so as to gain insight into ALTO’s function.