PRLR is regulated by ubiquitination of the activated receptor, leading to lysosomal degradation (Djiane et al. 1981, 1982, Lu et al. 2002). Recruitment of the SCFbeta-TrCP ubiquitin ligase complex enables receptor ubiquitination and internalization (Li et al. 2004). This limits the duration and intensity of receptor signaling. Deregulation of this negative control lead to pathological conditions including cancer (Swaminathan et al. 2008).