CDKL3 and cancer: Through direct phosphorylation on CDK4 T172, CDKL3 prevents ubiquitin-proteasomal degradation of CDK4 in cancer cells, thus preserving a sufficient amount of CDK4 for G1 phase “highway racing.” Though phosphorylation of T172 was uncovered previously as a demonstration of CDK4 activation (32, 33), the underlying mechanism remained obscure.