RB1 and Merkel cell skin cancer: In MCPyV integrated within MCC cells, the LTAg gene is affected by a truncating mutation or deletion to generate tLTAg, eliminating the C-terminus and rendering the virus non-replicative (101, 115, 145) while sparing the LXCXE binding motif (2, 146), which plays a critical role in LTAg-driven proliferation via inactivation of RB and subsequent activation of E2F cell cycle genes (2).