CDKN3 and melanoma: In contrast, in melanoma, where p16INK4A is frequently inactivated by mutation, depletion of TBX2 in both mouse and human melanoma cells leads to senescence associated with increased expression of CDKN1A encoding the p21 cyclin-dependent kinase inhibitor (CDKi), with TBX2 able to directly bind and repress the CDKN1A promoter (Prince et al. 2004; Vance et al. 2005).