Because different ubiquitin ligase proteins have been implicated in mediating the ubiquitination of the IGF-IR (28, 33, 37, 39) we can speculate that different complexes may have different abilities in promoting either polyubiquitination or multiubiquitination of the receptor depending on either cell background or tumor model thus differentially affecting receptor sorting, stability, and biological activity (Figure 1). This evidence concerns the gene IGF1R and neoplasm.