RNF168 and cancer: Aberrations of both TRIP12 and UBR5 have been described in certain types of cancer (Clancy et al., 2003; O’Brien et al., 2008; Yoo et al., 2011), and elevated RNF168 protein levels and expanded 53BP1 foci were found in a subset of advanced human papillomavirus (HPV)-positive tumors (Gudjonsson et al., 2012), suggesting that the homeostasis of ubiquitin signaling achieved through regulation of RNF168 levels as illustrated here could be subverted during tumorigenesis.