 There are other INK4 genes on other chromosomes, however these are not linked to cancer, and so their functions are not likely to be overlapping.An important cyclin-dependent substrate is the retinoblastoma protein Rb, which is phosphorylated in late gap 1 phase (G1 phase), allowing G1 exit.The Rb protein limits cell proliferation by blocking the activity of E2F transcription factors, which activate the transcription of genes needed for DNA replication.