RB1 and melanoma: For instance, lossof the melanoma predisposition gene p16INK4a, detectably weakenedthe pRb-pathway and the senescence program in melanocytes by inhibiting thepRb-dependent development of SAHF [34].Considering that the CDK inhibitors p16INK4a and p21Waf1were both potently induced in melanocytes in response to N-RASQ61Kexpression (see Figure 1C), we wanted to establish whether the function of p16INK4ain the formation of SAHF was specific to this CDK inhibitor or whether anothersenescence-associated CDK inhibitor p21Waf1 was equivalent inactivity.